Microbiome and its relevance to indigenous inflammatory bowel diseases in China.

BACKGROUND: Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an unknown etiology. Although dysbiosis is implicated in its pathogenesis, deep sequencing and oral microbiota study in Chinese IBD patients is absent. AIM: To explore the role of oral / intestinal microbiota in patients with IBD and the potential associations therein. METHODS: Clinical data, fecal and saliva samples were harvested from 80 patients with IBD (Crohn's disease, CD, n = 69; Ulcerative colitis, UC, n = 11) and 24 normal controls. Microbiomics (16S rRNA sequencing and 16S rRNA full-length sequencing) were used to detect and analyze the difference between IBD patients and normal control. RESULTS: Compared with normal controls, a higher abundance of the intestinal Shigella spp. (Shigella flexneri and Shigella sonnei, which were positively relate to the severity of IBD), lower abundance of intestinal probiotics (Prevotella, Faecalibacterium and Roseburia), and higher abundance of oral Neisseria were present in IBD patients with microbiome. The higher inflammation-related markers, impaired hepatic and renal function, and dyslipidaemia were present in patients with IBD. A higher intake of red meat and increased abundance of Clostridium in the gut were found in CD patients, while the elevated abundance of Ruminococcus in the gut was showed in UC ones. The bacterial composition of saliva and fecal samples was completely different, yet there was some correlation in the distribution of dominant probiotics. CONCLUSION: Enteric dysbacteriosis and the infections of pathogenic bacteria (Shigella) may associate with the occurrence or development of IBD.

The predictive value of modified-DeepSurv in overall survivals of patients with lung cancer.

The traditional prognostic model may induce the possibility of incorrect assessment of mortality risk under the assumption of linearity. It is urgent to develop a non-linearity precise prognostic model for achieving personalized medicine in lung cancer. In our study, we develop and validate a prognostic model "Modified-DeepSurv" for patients with lung carcinoma based on deep learning and evaluate its value for prognosis, while Cox proportional hazard regression was used to develop another model "CPH." The C-index of the Modified-DeepSurv and CPH was 0.956 (95% confidence interval [CI]: 0.946-0.974) and 0.836 (95% CI: 0.774-0.896), respectively, in the training cohort, while the C-index of the Modified-DeepSurv and CPH was 0.932 (95%CI: 0.908-0.964) and 0.777 (95%CI: 0.633-0.919), respectively, in the test dataset. The Modified-DeepSurv model visualization was realized by a user-friendly graphic interface. Modified-DeepSurv can effectively predict the survival of lung cancer patients and is superior to the conventional CPH model.

Thoracoscopic resection of a cavernous haemangioma of anterior mediastinum: case report and literature review.

Background: Mediastinal haemangioma is a rare type of tumour and accounts for ≤0.5% of all mediastinal tumours. Mediastinal haemangioma is often nonspecific upon examination by imaging. Mediastinal haemangioma diagnosis is difficult to confirm before surgery because the characteristic features of diagnostic imaging are poor, and these lesions are extremely rarely encountered in clinical practice. Case Description: We herein report a case of thoracoscopic resection of a cavernous haemangioma in the anterior mediastinum. A 40-year-old man was referred to our hospital for a health examination. A chest computed tomography scan showed a mass with irregular contrast enhancement and a smooth surface. Using video-assisted thoracoscopic surgery, the tumour was completely extirpated and confirmed histologically to be a cavernous haemangioma. The patient recovered well, was discharged, he has since had no recurrences, and continues to be closely monitored as an outpatient. Conclusions: Mediastinal haemangiomas, a rare type of mediastinal tumour, are typically benign and located in the anterior mediastinum, and lack specific symptoms and relevant imaging features. We found that minimally invasive thoracoscopic resection provided a satisfactory view and facilitated correct handling of a mediastinal cavernous haemangioma. Although such tumours are mostly benign and the prognosis is good, we recommend aggressive surgical management to avoid missing malignant lesions.

CD73/NT5E-mediated ubiquitination of AURKA regulates alcohol-related liver fibrosis via modulating hepatic stellate cell senescence.

Alcohol-related liver disease (ALD) is the most common chronic liver disease worldwide; however, no effective treatment to prevent the progression of alcohol-related liver fibrosis (ALF) is available. CD73/NT5E, a nucleotidase, controls cellular homeostasis by combining extracellular purinergic signaling with intracellular kinase activity and gene transcription and is associated with cell proliferation, differentiation, and death. In this study, we demonstrated that CD73/NT5E had a more significant regulatory effect on the activation, proliferation, and apoptosis of HSCs compared with that of CD39/ENTPD1. We examined the expression of CD73/NT5E in the normal and fibrotic human livers. The absence of CD73/NT5E was protective in mouse models of ALF. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that CD73/NT5E overexpression was related to the p53 signaling pathway, which regulates cell senescence. Proteins interacting with p53 were predicted using the STRING database. The overlap between proteomic analysis and STRING databases was for Aurora kinase A (AURKA), a cell cycle-regulated kinase. Coimmunoprecipitation (co-IP) assay and molecular docking confirmed that CD73/NT5E directly interacted with AURKA. We found that overexpression of CD73/NT5E inhibited AURKA ubiquitination, whereas p53 signaling was downregulated. Mechanistically, CD73/NT5E regulated ALF and the activation and senescence of stellate cells by binding to AURKA. These findings indicate that CD73/NT5E is a potential therapeutic target for ALF.

CD73-Adenosine A1R Axis Regulates the Activation and Apoptosis of Hepatic Stellate Cells Through the PLC-IP3-Ca2+/DAG-PKC Signaling Pathway.

Alcohol-related liver fibrosis (ALF) is a form of alcohol-related liver disease (ALD) that generally occurs in response to heavy long-term drinking. Ecto-5'-nucleotidase (NT5E), also known as CD73, is a cytomembrane protein linked to the cell membrane via a GPI anchor that regulates the conversion of extracellular ATP to adenosine. Adenosine and its receptors are important regulators of the cellular response. Previous studies showed that CD73 and adenosine A1 receptor (A1R) were important in alcohol-related liver disease, however the exact mechanism is unclear. The aim of this study was to elucidate the role and mechanism of the CD73-A1R axis in both a murine model of alcohol and carbon tetrachloride (CCl4) induced ALF and in an in vitro model of fibrosis induced by acetaldehyde. The degree of liver injury was determined by measuring serum AST and ALT levels, H & E staining, and Masson's trichrome staining. The expression levels of fibrosis indicators and PLC-IP3-Ca2+/DAG-PKC signaling pathway were detected by quantitative real-time PCR, western blotting, ELISA, and calcium assay. Hepatic stellate cell (HSC) apoptosis was detected using the Annexin V-FITC/PI cell apoptosis detection kit. Knockdown of CD73 significantly attenuated the accumulation of α-SMA and COL1a1 damaged the histological architecture of the mouse liver induced by alcohol and CCl4. In vitro, CD73 inhibition attenuated acetaldehyde-induced fibrosis and downregulated A1R expression in HSC-T6 cells. Inhibition of CD73/A1R downregulated the expression of the PLC-IP3-Ca2+/DAG-PKC signaling pathway. In addition, silencing of CD73/A1R promoted apoptosis in HSC-T6 cells. In conclusion, the CD73-A1R axis can regulate the activation and apoptosis of HSCs through the PLC-IP3-Ca2+/DAG-PKC signaling pathway.

[Analysis of Influence on Single Eythrocyte Injury Caused by Oscillating Boundary Flow Field].

The implantable axial blood pump, driven by external electromagnet, is studied recently. It oscillats when it is running because of the elastic implanted environment and driving force disequilibrium, etc. In this paper, a model of single erythrocyte in vibrated flow field was built to simulate the deformation and force of the erythrocyte. By using the mechanical injury principle of blood in blood pump, we studied the injury of a single erythrocyte resulted from oscillating boundary flow field. The research results indicated that the shape of the erythrocyte, force and velocity field nearby, which are affected by oscillating boundary flow field, all cause injury to the erythrocyte. All the researches shown in the present paper are expected to provide theoretical foundation for lightening hemolysis by the blood pump.

Antibacterial and laxative activities of strictinin isolated from Pu'er tea (Camellia sinensis).

Strictinin, the major phenolic compound in Pu'er teas produced from young leaves and buds of wild trees, was isolated to evaluate its antibacterial and laxative activities. The minimum inhibitory concentrations of strictinin against Propionibacterium acnes and Staphylococcus epidermidis were determined as 250 µM and 2000 µM, respectively, apparently higher than those of several antibiotics commonly used for bacterial infections. The additive and synergistic effects on the inhibitory activities of strictinin combined with other commercial antibiotics were observed in two bacteria tested in this study via the analysis of fractional inhibitory concentrations. Laxative activity was observed on defecation of the rats fed with strictinin. Further analysis showed that the laxative effect of strictinin was presumably caused by accelerating small intestinal transit, instead of enhancing gastric emptying, increasing food intake, or inducing diarrhea in the rats. Taken together with the antiviral activities demonstrated previously, it is suggested that strictinin is one of the active ingredients responsible for the antiviral, antibacterial, and laxative effects of wild Pu'er tea, and has the potential to be developed as a mild natural substitute for antibiotics and laxatives.

Risk-cost-benefit analysis for transportation corridors with interval uncertainties of heterogeneous data.

Access management, which systematically limits opportunities for egress and ingress of vehicles to highway lanes, is critical to protect trillions of dollars of current investment in transportation. This article addresses allocating resources for access management with incomplete and partially relevant data on crash rates, travel speeds, and other factors. While access management can be effective to avoid crashes, reduce travel times, and increase route capacities, the literature suggests a need for performance metrics to guide investments in resource allocation across large corridor networks and several time horizons. In this article, we describe a quantitative decision model to support an access management program via risk-cost-benefit analysis under data uncertainties from diverse sources of data and expertise. The approach quantifies potential benefits, including safety improvement and travel time savings, and costs of access management through functional relationships of input parameters including crash rates, corridor access point densities, and traffic volumes. Parameter uncertainties, which vary across locales and experts, are addressed via numerical interval analyses. This approach is demonstrated at several geographic scales across 7,000 kilometers of highways in a geographic region and several subregions. The demonstration prioritizes route segments that would benefit from risk management, including (i) additional data or elicitation, (ii) right-of-way purchases, (iii) restriction or closing of access points, (iv) new alignments, (v) developer proffers, and (vi) etc. The approach ought to be of wide interest to analysts, planners, policymakers, and stakeholders who rely on heterogeneous data and expertise for risk management.

Pilot analysis of the plasma metabolite profiles associated with emphysematous Chronic Obstructive Pulmonary Disease phenotype.

The current pilot study examined the hypothesis that cigarette smokers who developed an emphysematous phenotype of Chronic Obstructive Pulmonary Disease (COPD) were associated with distinctive patterns in their corresponding metabolomics profile as compared to those who did not. Peripheral blood plasma samples were collected from 38 subjects with different phenotypes of COPD. They were categorized into three groups: healthy non-smokers (n=16), smokers without emphysema (n=8), and smokers with emphysema (n=14). Ultra High Performance Liquid Chromatography/quadrupole-Time-of-Flight Mass Spectrometry techniques were used to identify a large number of metabolite markers (3534). Unsupervised clustering analysis accurately separated the smokers with emphysema from others without emphysema and demonstrated potentials of this metabolomics data. Subsequently predictive models were created with a supervised learning set, and these predictive models were found to be highly accurate in identifying the subjects with the emphysematous phenotype of COPD with excellent sensitivity and specificity. Our methodology provides a preliminary model that differentiates an emphysematous COPD phenotype from other COPD phenotypes on the basis of the metabolomics profiles. These results also suggest that the metabolomics profiling could potentially guide the characterization of relevant metabolites that leads to an emphysematous COPD phenotype.