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Gremlin has been reported to regulate inflammation and osteogenesis. Periodontitis is a destructive disease degenerating periodontal tissues, therefore leads to alveolar bone resorption and tooth loss. Based on the importance of Gremlin's bio-activity, the aim of this study is to, in vivo and in vitro, unveil the function of Gremlin in regulating the development of periodontitis and its consequent effects on alveolar bone loss.Clinical specimens were used to determine the expression of Gremlin in periodontal tissues by immunohistochemical staining and western blot. Then utilizing the rat periodontitis model to investigate the function of gremlin-regulated nuclear factor-kappa B (NF-κB) pathway during the development of periodontal inflammation and the alveolar bone loss. Last, the regulation of the osteogenesis of human periodontal ligament stem cells (hPDLSCs) by Gremlin under inflamed condition was analyzed by alkaline phosphatase (ALP) and alizarin red staining (ARS).We found clinically and experimentally that the expression of Gremlin is markedly increased in periodontitis tissues. Interestingly, we revealed that Gremlin regulated the progress of periodontitis via regulating the activities of NF-κB pathway and interleukin-1β (IL-1β). Notably, we observed that Gremlin influenced the osteogenesis of hPDLSCs. Thus, our present study identified Gremlin as a new key regulator for development of periodontitis.Our current study illustrated that Gremlin acts as a crucial mediator and possibly serves as a potential diagnostic marker for periodontitis. Discovery of new factors involved in the pathophysiology of periodontitis could contribute to the development of novel therapeutic treatment for the disease.

Zhitong Li1 *, Lifei Pan1 *, Yawen Deng,1 Quanbo Liu,2 Tesfaldet H Hidru,1 Fei Liu,1 Chenglin Li,1 Tao Cong,1 Xiaolei Yang,1 Yunlong Xia1 1Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaolei Yang; Yunlong Xia, Email 15942456079@yeah.net; yunlong_xia@126.comPurpose: Left atrial thrombus (LAT)/left atrial spontaneous echo contrast (LASEC) still exists in CHA2DS2-VASc score-defined low/borderline risk population. The purpose of this study is to explore the risk factors that associate with LAT/SEC and to create a nomogram to predict LAT/SEC risk in NVAF patients with low/borderline CHA2DS2-VASc scores.Patients and Methods: A total of 834 NVAF patients with complete data on transesophageal echocardiography (TEE) were included in this study. Univariate and multivariate logistic regression analyses were performed to identify the risk factors that associate with LAT/SEC, and a nomogram was established based on the results. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis were performed to verify the predictive power of nomogram.Results: The rates for LAT/SEC for the training and validation cohorts were 84 (14.7%) and 30 (11.4%), respectively. Independent factors including age, left ventricular ejection fraction (LVEF), left atrial diameter (LAD), smoke, non-paroxysmal AF (NPAF), and E/e’ were considered to construct the nomogram for LAT/SEC. The AUC for nomogram was 0.839 and 0.811 in the training and validation cohorts, respectively. The calibration and decision curve analysis showed that the nomogram had a good prediction capacity and would be clinically useful.Conclusion: Age, LVEF, LAD, smoke, NPAF, and E/e’ are independently associated with LAT/SEC in NVAF patients with low/borderline CHA2DS2-VASc scores. The nomogram that incorporates these six variables effectively predict LAT/SEC risk in NVAF patients with low/borderline CHA2DS2-VASc scores.Keywords: left atrial thrombus, spontaneous echo contrast, atrial fibrillation, nomogram, CHA2DS2-VASc score

In this study, a Streptomyces strain was isolated from the soil samples of Yanghu Wetland Park in Changsha, Hunan Province. This strain showed excellent antimicrobial activity against 10 fish pathogens, as indicated by the results of the agar-diffusion and oxford cup assays. After 16s rDNA sequencing and physiological & biochemical analyses, it was identified as Streptomyces amritsarensis, namely for S. amritsarensis N1-32. Cytotoxicity test was performed, and the results exhibited that this strain had no toxicity to hepatic L8824 cell line from grass carp liver. The diets supplemented strain N1-32 at concentrations of 1 × 107 cfu/g and 1 × 109 cfu/g was used to feed fish. After 28 days, the expression levels of antioxidant-related genes Nrf2 and Keap1 in the liver and spleen were significantly up-regulated, and the expression of immune-related gene IgM was notably increased in the liver, kidney, head-kidney, and spleen. Toll-like receptor 4 (TLR4) gene expression was up-regulated in the spleen, and TLR4, myeloid differentiation factor 88 (MyD88) gene were up-regulated in the kidney. The survival rate of grass carp was significantly improved after pathogen infection. Whole-genome analysis of N1-32 showed that the strain harbored related genes, capability for producing substances that enhance the immunity of grass carp and inhibit pathogens. A total of 22 gene clusters were identified in the genome, including 5 terpene gene clusters, 4 nonribosomal peptide-synthetase (NRPS) gene clusters and 2 lantipeptide gene clusters. In summary, these results showed that strain N1-32 as a feed additive could regulate grass carp immunity and enhance the resistance of grass carp against fish pathogens.

The current treatment of radiation-induced coronary artery disease (RCAD) is comparable to that of generic coronary artery disease (CAD); however, the outcomes of these treatment measures have not been fully examined in RCAD. A 33-year-old woman, without conventional cardiovascular risk factors, presented with left main coronary artery (LMCA) lesions. At the age of 26, she received mediastinal radiation therapy (RT) to treat mixed cellularity Hodgkin lymphoma. One BiodivYsio 3.5 × 18 mm stent was implanted at the LMCA site. At the age of 38, the patient was treated by balloon dilatation because of approximately 50% in-stent stenosis. At the last follow-up in February 2018, when the patient was 51 years old, she no longer complained of chest pain. Coronary angiography showed no de novo or in-stenosis lesions, although optical coherence tomography showed mild neointimal proliferation, calcific plaque, small ruptured intima, and several uncovered struts. The experience of treating this case may shed some light on coronary stenting in coronary lesions caused by RCAD.

This study evaluated the inhibition and interaction of Bacillus velezensis BvL03 as a probiotic agent against Aeromonas hydrophila. Strain BvL03 isolated from sediment samples of fish ponds had excellent antimicrobial activity against several fish pathogenic bacteria, especially Aeromonas, including A. hydrophila, A. veronii, A. caviae, and A. sobria. The successful amplification of lipopeptide antimicrobial chemical biosynthetic genes, including iturin family (ituA, ituB, and ituD), bacillomycin family (bacA, bacD, and bacAB), surfactin family (srfAB, srfC, and srfAA), and subtilosin family (albF and sunT) from the genome of BvL03 strain, confirmed its predominant antimicrobial activity. The challenge test suggested that BvL03 significantly decreased fish mortality when challenged with A. hydrophila, which had a cumulative mortality of 12.5% in the treatment group. Toxicity and hemolytic activity of A. hydrophila after co-cultured with BvL03 were relieved as confirmed by the cell experiments, when the initial inoculated concentration of BvL03 was 109 cfu/mL or higher. Moreover, the BvL03 strain labeled with GFP protein (BvL03-GFP) and AhX040 strain labeled with mCherry protein (AhX040-mCherry) were injected into grass carps. The fluorescence levels were monitored by using In Vivo Imaging System (IVIS), in which the green color was steadily increasing, whereas the red color was gradually weakening. Whole genome sequencing revealed that strain BvL03 possesses 15 gene clusters related to antibacterial compounds, including 5 NRPS gene clusters and 3 PKS gene clusters. These results suggested that B. velezensis BvL03 has the potential to be developed as a probiotic candidate against A. hydrophila infection in aquaculture.

The current treatment of radiation-induced coronary artery disease (RCAD) is comparable to that of generic coronary artery disease (CAD); however, the outcomes of these treatment measures have not been fully examined in RCAD. A 33-year-old woman, without conventional cardiovascular risk factors, presented with left main coronary artery (LMCA) lesions. At the age of 26, she received mediastinal radiation therapy (RT) to treat mixed cellularity Hodgkin lymphoma. One BiodivYsio 3.5 × 18 mm stent was implanted at the LMCA site. At the age of 38, the patient was treated by balloon dilatation because of approximately 50% in-stent stenosis. At the last follow-up in February 2018, when the patient was 51 years old, she no longer complained of chest pain. Coronary angiography showed no de novo or in-stenosis lesions, although optical coherence tomography showed mild neointimal proliferation, calcific plaque, small ruptured intima, and several uncovered struts. The experience of treating this case may shed some light on coronary stenting in coronary lesions caused by RCAD.

Background Coronary artery ectasia (CAE) is an uncommon finding in patients undergoing coronary angiography and acute myocardial infarction is an extremely uncommon condition in the presence of coronary artery ectasia. To date, 50 gene variants associated with coronary artery disease have been identified, but none appear to be related to coronary artery ectasia. Case presentation This is a rare case of Coronary artery ectasia which is considered to be related to Gene variations in potassium voltage-gated channel subfamily H member 1, KCNH1 (encoding a protein designated ether à go-go, EAG1 or KV10.1). Conclusion Occurrence of Acute myocardial infarction in patient with coronary artery ectasia after diarrhea is a very rare condition and involvement of KCNH1 gene mutation which is described in this case report.

In physiology conditions, the crosstalk of signaling pathways has been considered to extend the functions of individual pathways and results in a more complex regulatory network. The Wnt3a/β-catenin and NF-κB signaling pathways have been demonstrated involving in apical periodontitis (AP). As AP progresses, ultimately causes tooth loss. In the present study, we investigate the contribution of the crosstalk between the Wnt3a/β-catenin and NF-κB signaling pathways to the development of AP. Clinically, utilizing 60 human AP and healthy tissues (30 samples for each group), we found that the expression levels of Wnt3a/β-catenin and NF-κB were elevated in the Ap tissues compared to that in the healthy group. To further study the roles of Wnt3a/β-catenin and NF-κB signaling pathways in the development of AP, and the contribution of the crosstalk between these two signaling pathways to AP, we established the AP animal model and observed that, first, both pathways are activated in the AP group compared to the control group. Interestingly, by immunoprecipitation and western blot experiments, we revealed that there is greater interaction between NF-κB (phorspho-p65) and β-catenin in AP tissues compared to the control tissues. Importantly, when the NF-κB signaling pathway was blocked by its inhibitor, pyrrolidine dithiocarbamate (PDTC), the activity of the Wnt3a/β-catenin signaling pathway was abolished, and consequently led to the attenuation of the inflammation response in LPS-induced human periodontal ligament cells (hPDLCs). Thus, our data indicate that the crosstalk between Wnt3a/β-catenin and NF-κB signaling pathway contributes to the development of AP, and provide a therapeutic strategy for the treatment of AP as well.

Gut microbiota are known to play an important role in health and nutrition of the host and have been attracting an increasing attention. Farming of new lineages of grass carp and crucian carp has been developed rapidly as these species were found to outperform indigenous ones in terms of growth rate and susceptibility to diseases. Despite this rapid development, no studies have addressed the characteristics of their gut microbiota as a potential factor responsible for the improved characteristics. To reveal whether microbiomes of the new lineages are different from indigenous ones, and therefore could be responsible for improved growth features, intestinal microbiota from the new lineages were subjected to high‐throughput sequencing. While the phyla Firmicutes, Fusobacteria and Proteobacteria were representing the core bacterial communities that comprised more than 75% in all fish intestinal samples, significant differences were found in the microbial community composition of the new linages versus indigenous fish populations, suggesting the possibility that results in the advantages of enhanced disease resistance and rapid growth for the new fish lineages. Bacterial composition was similar between herbivorous and omnivorous fish. The relative abundance of Bacteroidetes and Actinobacteria was significantly higher in omnivores compared to that of herbivores, whereas Cetobacterium_sp. was abundant in herbivores. We also found that the gut microbiota of freshwater fish in the Dongting lake area was distinct from those of other areas. Network graphs showed the reduced overall connectivity of gut bacteria in indigenous fish, whereas the bacteria of the new fish lineage groups showed hubs with more node degree. A phylogenetic investigation of communities by reconstruction of unobserved states inferred function profile showed several metabolic processes were more active in the new lineages compared to indigenous fish. Our findings suggest that differences in gut bacterial community composition may be an important factor contributing to the rapid growth and high disease resistance of the new fish lineages., Our results are the first to reveal the gut microbial composition in the new lineages of grass carp and crucian carp from the Dongting lake area and differences of gut microbiota between new lineages and the indigenous fish populations. These findings may offer an understanding why the new lineages could grow faster and possess higher disease resistance. We also concluded that the gut microbiota of freshwater fish in the Dongting lake area was distinct from those of other areas.

Probiotic-feeding continues to be a promising strategy to control the bacterial pathogens in aquaculture. A new Pediococcus pentosaceus strain (SL001) was isolated from 1000s of soil samples, which exhibited wide antimicrobial spectrum of against fish pathogens, involving Aeromonas hydrophila, Aeromonas veronii, Aeromonas sobria, Edwardsiella tarda, Lactococcus garvieae, and Plesiomonas shigelloide. The challenge test against A. hydrophila showed that the survival rate of SL001-supplemented group was significantly higher than that of control group (P < 0.05). Moreover, SL001 could stably colonize in gut of grass carp and increased mucus-secreting goblet cells and extended intestinal villi could be observed in SL001-supplemented group (P < 0.05). Feeding with SL001 supplemented diet could significantly enhance the growth rate (P < 0.05) and markedly affect gut microbiota structure of grass carps, resulting in reduced potential pathogens and increased potential probiotics. Furthermore, feeding grass carps with SL001 caused the up-regulated expression of insulin-like growth factor (IGF-1 and IGF-2) and down-regulated expression of myostatin (MSTN-1 and MSTN-2) (P < 0.05), which probably also account for the increased growth rate of SL001-fed group. Meanwhile, relative mRNA expression levels of immune-related genes in liver, spleen, and head kidney were analyzed in grass carps after feeding for 30 days with SL001 supplemented diets. In all three immune organs, the expression levels of immunoglobulin M (IgM) and complement 3 (C3) were significantly increased (P < 0.05), whereas the interleukin-8 (IL-8) was down-regulated (P < 0.05). Besides, whole genome sequencing revealed several probiotics properties of SL001, including organic acid synthesis, bacteriocin synthesis (coagulin), superoxide dismutase, and digestive enzymes. In conclusion, P. pentosaceus SL001 which could enhance immunity and promoter growth rate of grass carps, is prospective to be used as a dietary probiotic in freshwater fish aquaculture.

Citrobacter freundii, a common pathogen of freshwater fish, severely restricts the sustainable development of the aquaculture industry. In this study, the novel C. freundii strain CFC202 was isolated from the intestines of crucian carp, which was annotated with three virulence factors related to promoting bacterial colonization and causing anemia by the whole genome analysis. We found that the strain adhered to the surface of hepatic L8824 cells, and actin aggregation occurred at the adhesion site of the strain. Then, C. freundii was fluorescently labelled and imaged the distribution of crucian carp under an In Vivo Imaging System (IVIS) during natural infection. The results showed that this strain mainly gathered in the intestines of crucian carp, and the intestinal villi were severely damaged by TEM. From the results of histopathological examination, the intestinal mucosa was obviously shed and various organs were damaged. Hence, we speculated that C. freundii could cause attaching and effacing (A/E) lesions to fish cells, which in turn caused pathological changes to various organs. Moreover, we constructed C. freundii ghost (CFG) and evaluated their immune effects by oral and injection immunization in crucian carp. Compared with the non-immunized group, non-specific immune indicators (ACP, AKP, SOD, and LZM), agglutination antibody titres of the serum, and the expression of immune-related genes (TNF-α and IL-6) of the head kidney and spleen were significantly increased in the immunized group (P

A series of SrZn2(PO4)2:Eu3+,Tb3+, Li+ phosphors were prepared by the solid-state method. The characteristic results indicate that there is effective energy transfer from Tb3+ to Eu3+ when excited at 393 nm, and Li+ can efficiently enhances emission of Eu3+ for SrZn2(PO4)2:Eu3+, Tb3+. The optimal contents of Tb3+, Li+ are 0.05 and 0.048, which the corresponding sample is SrZn2(PO4)2:0.02Eu3+, 0.05 Tb3+, 0.048Li+ and its I (peak area) of PL is as high as 3.36 times of that without Li+. SrZn2(PO4)2:0.02Eu3+, 0.05 Tb3+, 0.048Li+ is a potential red-emitting phosphor for UV-based white LED.

This study aims at assigning elective surgical cases into a set of operating rooms by taking into account both the efficiency and effectiveness of the operating theatre. Besides the cost considered in most of the studies found in the literature, the nurses preferences of cooperation and the balancing of their technical skill training are also considered. The targeted problem is firstly formulated as a multi-objective mixed-integer mathematical programming. Afterwards, the nonlinear constraints are transformed into a mixed-integer linear programming by linearizing the nonlinear constraints and all objectives are weighted and integrated into one general objective. The final mixed-integer linear programming is solved by CPLEX with data collected from a medium-size specialty hospital in China. Experimental results show that CPLEX can solve the model for the problems with up to five operating rooms though the execution time increases dramatically when the size of the problem becomes larger. The comparison between the optimal solution and the actual performance of the involved hospital shows that our solution can greatly improve the efficiency of the operating theatre for all considered objectives and thus can help the hospital managers to improve their work.

Delirium is thought to be associated with systemic inflammatory response. However, its association with the most widely used inflammatory biomarker C-reactive protein (CRP) has not been well established. We aimed to examine whether CRP on intensive care unit (ICU) entry was associated with subsequent development of delirium.This prospective observational study was conducted in a mixed 24-bed ICU in a tertiary teaching hospital.All patients admitted to the ICU from February 2011 to June 2012 were screened for eligibility. Demographic data and clinical characteristics of included patients were recorded. Patients were screened for the presence of delirium by using the tool Confusion Assessment Method for the ICU (CAM-ICU). C-reactive protein was obtained on ICU entry and 24 hours thereafter. Eligible patients were followed up for 28 days or until death. Univariate and multivariate analyses were performed to evaluate independent risk factors for delirium. Clinical outcome included the length of stay (LOS) in the ICU, 28-day mortality, and duration of mechanical ventilation. Two-tailed P.05 was considered statistically significant.A total of 223 patients were included during study period. In univariate analysis, patients with delirium showed significantly higher CRP values than those without (120.5 vs 57.5 mg/L; P = .0001). By adjusting for confounding variables (including age, sex, Acute Physiology and Chronic Health Evaluation II, intubation, living alone, physical restraint, alcohol drinking, smoking, type of medical condition, and hospital LOS before ICU admission) in logistic regression model, CRP remained an independent predictor of delirium (odds ratio, 1.07; 95% confidence interval, 1.01-1.15). As compared with nondelirious patients, those with delirium showed longer LOS in ICU (13 vs 5 days; P.001) and duration of mechanical ventilation (6 vs 1 days; P.001). An increase in CRP greater than 8.1 mg/L within 24 hours was associated with 4-fold increase in the risk of delirium (odds ratio: 4.47, 95% confidence interval, 1.28-15.60).C-reactive protein measured on ICU entry and its changes within 24 hours are risk indicators of delirium. Further studies exploring the treatment of delirium according to CRP levels are warranted.

Context Delirium is prevalent in the intensive care unit (ICU) and has been associated with negative clinical outcomes. However, a quantitative and systematic assessment of published studies has not been conducted. Objective Meta-analysis of clinical observational studies was performed to investigate the association between delirium and clinical outcomes. Data sources and study selection Relevant studies were identified by investigators from databases including Medline, Embase, OVID and EBSCO from inception to May 2012. Studies that reported the association of delirium with clinical outcomes in critical care setting were included. Data extraction Data were extracted independently by reviewers and summary effects were obtained using random effects model. Data synthesis Of the 16 studies included, 14 studies involving 5891 patients reported data on mortality, and delirious patients had higher mortality rate than non-delirious patients (odds ratio [OR]: 3.22; 95% confidence interval [CI]: 2.30–4.52). Delirious patients had higher rate of complications (OR: 6.5; 95% CI: 2.7–15.6), and were more likely to be discharged to skilled placement (OR: 2.59; 95% CI: 1.59–4.21). Furthermore, patients with delirium had longer length of stay in both ICU (weighted mean difference [WMD]: 7.32 days; 95% CI: 4.63–10.01) and hospital (WMD: 6.53 days; 95% CI: 3.03–10.03), and they spent more time on mechanical ventilation (WMD: 7.22 days; 95% CI: 5.15–9.29). Conclusion Delirium in critically ill patients is associated with higher mortality rate, more complications, longer duration of mechanical ventilation, and longer length of stay in ICU and hospital.