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Background Macro-reentrant atrial tachycardias (MATs) are a common complication after cardiac valve surgery. The MAT types and the effectiveness of MAT ablation might differ after different valve surgery. Data comparing the electrophysiological characteristics and the ablation results of MAT post-tricuspid or mitral valve surgery are limited. Methods Forty-eight patients (29 males, age 56.1 ± 13.3 years) with MAT after valve surgery were assigned to tricuspid valve (TV) group (n = 18) and mitral valve (MV) group (n = 30). MATs were mapped and ablated guided by a three-dimensional navigation system. The one-year clinical effectiveness was compared in two groups. Results Nineteen MATs were documented in TV group, including 16 cavo-tricuspid isthmus (CTI)-dependent AFL and 3 other MATs at right atrial (RA) free wall, RA septum and left atrial (LA) roof. Thirty-nine MATs were identified in MV group, including15 CTI-dependent AFL, 8 RA free wall scar-related, 2 RA septum scar-related, 8 peri-mitral flutter, 3 LA roof-dependent, 2 LA anterior scar-related, and 1 right pulmonary vein-related MAT. Compared with TV group, MV group had significantly lower prevalence of CTI-dependent AFL (38.5% vs. 84.2%), higher prevalence of left atrial MAT (35.9 vs.5.3%) and higher proportion of patients with left atrial MAT (40 vs. 5.6%), P = 0.02, 0.01 and 0.01, respectively. The acute success rate of MAT ablation (100 vs. 93.3%) and the one-year freedom from atrial tachy-arrhythmias (72.2 vs. 76.5%) was comparable in TV and MV group. No predictor for recurrence was identified. Conclusion Although the types of MATs differed significantly in patients with prior TV or MV surgery, the acute and mid-term effectiveness of MAT ablation was comparable in two groups. Trial registration: This study was registered as a part of EARLY-MYO-AF clinical trial at the website ClinicalTrials. gov (NCT04512222).

The establishment of the precision diagnosis and treatment system and the advent of the digital intelligence era have not only deepened people's understanding of liver cancer but also continuously improved the diagnosis and treatment methods of liver cancer. Cutting-edge computer technology represented by artificial intelligence (AI) has been used in the prediction, screening, diagnosis, treatment, and rehabilitation of liver cancer. The rise of AI has given new vitality to liver surgery, as well as individualized treatment experience and greater healing opportunities for patients. We focus on summarizing the latest applications and developments of AI in liver cancer diagnosis and treatment from six aspects: virtual assistants, medical imaging diagnosis, adjuvant therapy, risk and treatment response prediction, drug development and testing, and postoperative rehabilitation management. Especially in the two major aspects of medical imaging diagnosis and adjuvant therapy, the development and achievements of AI are gratifying. Finally, we put forward a view on the current challenges of AI in the precise diagnosis and treatment of liver cancer and how to promote its development, and we have a prospect for the future development direction.

Background Left atrial (LA) dysfunction is associated with morbidity and mortality. To the knowledge of the authors, the relationship of LA strain to long-term prognosis in participants with ST-segment elevation myocardial infarction (STEMI) is unknown. Purpose To evaluate LA strain as a long-term outcome predictor in STEMI in a prospective, multicenter cardiac MRI cohort. Materials and Methods Participants with STEMI who underwent primary percutaneous coronary intervention and cardiac MRI from 10 sites (EARLY-MYO-CMR registry, clinical trial number NCT03768453) were included. The parent study took place between August 2013 and December 2018. LA longitudinal strain and strain rate parameters were derived from cine cardiac MRI by using an in-house semiautomated method. Major adverse cardiac events (MACEs) were defined as cardiovascular death, myocardial reinfarction, hospitalization for heart failure, and stroke. The association between LA performance and MACE was evaluated by using time-dependent receiver operating characteristic analysis, Kaplan-Meier analysis, and multivariable Cox regression analysis. Results A total of 321 participants (median age, 59 years; age range, 27-75 years; 90% men) were included in this study. During median follow-up of 3.7 years, MACE occurred in 76 participants (23.7%). Participants with impaired reservoir (≤22%) and conduit strain (≤10%) had a higher risk of MACE than those with reservoir strain greater than 22% and conduit strain greater than 10% (P < .001). Reservoir strain (hazard ratio, 0.84; 95% confidence interval: 0.77, 0.91; P < .001) and conduit strain (hazard ratio, 0.81; 95% confidence interval: 0.73, 0.89; P < .001) were independent predictors for MACE after adjustment for known risk factors. Finally, LA reservoir and conduit strains provided incremental prognostic value over traditional outcome predictors (Uno C statistic comparing models, 0.75 vs 0.68; P = .04). Conclusion Assessment of left atrial strain, as a measure of left atrial function, provided incremental prognostic information to established predictors in ST-segment elevation myocardial infarction. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kawel-Boehm and Bremerich in this issue.

Background Mitral isthmus (MI) ablation was limited due to technical challenges in the index ablation for long‐standing persistent atrial fibrillation (LPeAF). The role of adjunctive MI ablation was controversial. Hypothesis MI block could be achieved in most patients undergoing repeat LPeAF ablation and was associated with favorable clinical outcomes. Methods Of 87 consecutively patients undergoing reablation for recurrent atrial tachyarrhythmias (ATa), 41 patients with residual MI conduction but without pulmonary vein reconnection or left atrial roof conduction were enrolled to treat recurrent atrial flutter (AFL) (n = 20) and AF (n = 21). After AFL ablation and AF cardioversion, MI conduction gaps (CGs) were mapped and closed. Results MI line was successfully blocked in 37 (90.2%) of 41 patients after closing 1.4 ± 0.5 CGs (31 endocardial CGs and 16 epicardial ones) in the initial MI lines. CGs were more often located at the endocardial sites close to the lateral ridge between left atrial appendage and left‐sided PVs, midportion of MI and at the epicardial breakthroughs within coronary sinus. At the end of 16.0 ± 1.9 months' follow‐up, 31 (83.8%) of 37 patients with MI block and 1 of 4 patients without MI block were free of further recurrence of ATa off anti‐arrhythmic drugs. MI block was positively associated with ATa‐free survival by Cox's regression analysis (hazard ratio [HR]: 0.012, 95% confidence interval [CI]: 0.000‐0.456, P = .02). Conclusions MI block could be achieved in the majority of patients during repeat ablation for LPeAF. MI block was associated with favorable clinical outcomes after LPeAF reablation.

Koi carp (Cyprinus carpio) are well-known and highly valuable fish in the international ornamental fish community that have been plagued by Aeromonas veronii infections in recent years. Some A. veronii infections are serious enough to cause death. Lactobacillus plantarum, a probiotic, is one of the most environmentally friendly and safe alternatives to antibiotics for use as a feed additive for aquatic animals such as fish. The present study investigated the effects of L. plantarum C20015 on growth performance, immune responses, and eradication of A. veronii infection in koi carp. During a 6-week feeding experiment in an indoor aquarium and a 14-day A. veronii artificial infection experiment, a control diet group was fed with untreated feed twice a day, while experimental groups were given different concentrations of L. plantarum in their feed. The results indicated that the specific growth rate and percent weight gain of fish were significantly higher in the experimental groups than in the control diet group (P < 0.05). The activity of superoxide dismutase (SOD), peroxidase (POD), and lysozyme (LZM) and the levels of IgM antibody were significantly higher in the L. plantarum–supplemented groups than in the control diet group, and the enzymatic activity in the 108 CFU/g C20015 group was higher than that in the 107 CFU/g C20015 and 109 CFU/g C20015 groups (P < 0.01). In contrast, alkaline phosphatase (AKP) activity in the experimental groups was the highest at 42 days. All fish in the control diet group died 7 days after A. veronii infection. After 14 days, the relative percent survival (%, RPS) of the fish in the L. plantarum–supplemented groups was significantly higher than that of the fish in the control group, and the 108 CFU/g C20015 group had the highest RPS. Therefore, we first reported that fish fed with 108 CFU/g of L. plantarum C20015 could promote food intake and growth for koi carp.

Direct stenting (DS) without pre-dilatation of the culprit lesion might improve myocardial perfusion and prognosis in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI); however, some studies report conflicting results. We investigated whether DS provides incremental myocardial benefits over conventional stenting (CS) in STEMI patients based on cardiac magnetic resonance imaging (CMR) measures. Reperfused patients who underwent CMR examinations within 1 week of STEMI onset were selected from a multicenter CMR registry of STEMI (NCT: 03768453). Patients were stratified into either a DS or CS group. Each group comprised 137 patients after 1:1 propensity score matching. Major adverse events (MACEs), including death, myocardial re-infarction, re-admission for heart failure, and stroke were noted during a median period of 44 months (interquartile range 32-58 months). DS was associated with larger (p = 0.007) and shorter (p = 0.005) stent sizes than CS. DS and CS achieved comparable angiographic TIMI-3 flow grades (p = 0.86) and myocardial blush grades (p = 0.70). There were no group differences regarding the incidence of CMR manifestations of microvascular dysfunction, including microvascular obstruction (MVO) (p = 0.89) and intramyocardial hemorrhage (p = 0.47), the extent of MVO (p = 0.21), infarction size (p = 0.83), or left ventricular ejection fraction (p = 0.57). Kaplan-Meier analysis revealed similar risks of MACEs (log rank p = 0.909), which occurred in 23.4% of DS and 26.3% of CS patients (p = 0.576). DS did not show any incremental benefits over CS on myocardial impairments as evaluated using CMR.Clinical Trial Registration: Clinicaltrials.gov, NCT: 03768453.

Given the serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with MRSA as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, a Sephadex G-75 column, a QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31405.48 Da by SDS-PAGE. LC-MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% homology with chitosanase Csn produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 μg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in In Vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability.

Proline-rich antimicrobial peptides (PR-AMPs) have attracted much interest as they target Gram-negative and do not act by lytic mechanisms. In this study, a novel hybrid peptide OM19R was designed based on the Oncocin and MDAP-2. OM19R showed specific and improved potency against Escherichia coli (E. coli), Salmonella and Shigella standard strains compared to parental peptides. The minimum inhibitory concentrations (MICs) ranged from 1 to 2 μM. However, the activity against Klebsiella pneumoniae (K. pneumoniae) was inhibited. The dependence of the SbmA protein for OM19R activity was also studied by a gene-knockout strain. The confocal laser scanning microscopy further revealed that OM19R could rapidly penetrate into E. coli cells without membrane damage. In summary, the hybrid peptide OM19R is a strong cell-selective antibacterial peptide and a promising specific antibacterial agent.

Association between microRNA (miRNA) expression signatures and atrial fibrillation has been evaluated with inconsistent findings in different studies. This study aims to identify miRNAs that actually play vital role in pathophysiological process of atrial fibrillation and explore miRNA-targeted genes and the involved pathways. Relevant studies were retrieved from the electronic databases of Embase, Medline, and Cochrane Library to determine the miRNA expression profiles between atrial fibrillation subjects and non-atrial fibrillation controls. Robustness of results was assessed using sensitivity analysis. Subgroup analyses were performed based on species, miRNA detection method, sample source, and ethnicity. Quality assessment of studies was independently conducted according to QUADAS-2. Bioinformatics analysis was applied to explore the potential genes and pathways associated with atrial fibrillation, which were targeted by differentially expressed miRNAs. Form of pooled results was shown as log10 odds ratios (logORs) with 95% confidence intervals (CI), and random-effects model was used. In total, 40 articles involving 283 differentially expressed miRNAs were reported. And 51 significantly dysregulated miRNAs were identified in consistent direction, with 22 upregulated and 29 downregulated. Among above-mentioned miRNAs, miR-223-3p (logOR 6.473; P Impact statement Atrial fibrillation (AF) is considered as the most common arrhythmia, and it subsequently causes serious complications including thrombosis and heart failure that increase the social burden. The definite mechanisms underlying AF pathogenesis remain complicated and unclear. Many studies attempted to discover the transcriptomic changes using microarray technologies, and the present studies for this hot topic have assessed individual miRNAs profiles for AF. However, results of different articles are controversial and not each reported miRNA is actually associated with the pathogenesis of AF. The present systematic review and meta-analysis identified that 51 consistently dysregulated miRNAs were associated with AF. Of these miRNAs, five miRNAs (miRNA-1-5p, miRNA-328, miRNA-29b, miRNA-21, and miRNA-223-3p) may act as novel biomarkers for AF. The findings could offer a better description of the biological characteristics of miRNAs, meanwhile might serve as new target for the intervention and monitoring AF in future studies.

BACKGROUND: Atrial fibrillation (AF) is quite prevalent in patient with chronic kidney disease (CKD). This study mainly investigated the net clinical benefit (NCB) property of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with AF and CKD by a pooled-analysis. METHODS: A comprehensive search of Medline, Embase, Cochrane Library and Clinical Trials.gov Website was performed for eligible randomized controlled trials (RCTs) reporting the efficacy and safety outcomes according to renal function of NOACs. Pre-specified outcomes and their number of patients needed to treat (NNT), including stroke/systemic embolism (SSE), major bleeding, and all-cause death, were evaluated using a random-effects model. NCB that balanced SSE and major bleeding was calculated using Singer’s method. RESULTS: Four phase III clinical trials including 70,952 patients were enrolled, 45,265 (64%) with CKD, and 25,687 (36%) without CKD; 41,942 (59%) taking NOACs and 29,010 (41%) taking warfarin. Risks of SSE [relative risk (RR): 0.80, 95% confidence interval (CI): 0.73–0.88, P

Isolation and characterization of a bacteriocin from Brevibacillus laterosporus DS-3 and its ability in producing antibacterial activity were examined in this study. We isolated 48 bacterial strains from different native ecological niches. Sources included lake water, soil, air, and food. Among the isolates from the soil sample, morphological and biochemical tests identified Brev. laterosporus DS-3, which showed great potential for bacteriocin production. It was purified by ammonium sulfate precipitation, then applied in a Sephadex G-15 gel filtration column connected to a purification of AKTA Pure (USA) and reverse phase chromatography. MALDI-TOF mass spectrometry indicated that bacteriocin DS-3 has a low molecular weight of 1592.579 Da. LNTLETEEWFFK was identified as the sequence by mass spectrometry analysis in tandem liquid chromatography and MASCOT research. This bacteriocin inhibited Gram-positive and Gram-negative bacteria and was effective against Methicillin-resistant Staphylococcus aureus (MRSA). Brev. laterosporus DS-3 present in here is thermostable and tolerant to extreme pH. However, inactivation of its antibacterial activity was observed when treated with papain and trypsin but not pepsin, proteinase K, and catalase.

The present study evaluated the antibacterial activity and mode of action of fibrauretine on Escherichia coli (E. coli) and Staphylococcus aureus, and synergistic effect with kanamycin against multi-drug resistant E. coli. The fibrauretine exhibited inhibitory effect on the growth of the tested bacteria with minimum inhibitory concentration (MIC) and minimum bactericidal concentration of 2.5–5 and 5–10 mg/ml, respectively. Morphological changes of cell microstructure were observed after adding fibrauretine at MIC. The mode of action was further confirmed by measuring release of 260-nm absorbing materials and extracellular potassium ions. Checkerboard dilution test suggested that fibrauretine exhibited synergistic activity when combined with kanamycin (FICI ranging from 0.5625 to 0.625). Our results indicated that fibrauretine exerted synergistic effect with kanamycin and its antibacterial mode of action mainly attributed to disruption of cell membrane integrity.

Trueperella pyogenes (T. pyogenes) is a worldwide known pathogen of domestic ruminants and pigs causing a wide variety of infections. The objective of this study was to report the presence of major virulence genes in T. pyogenes isolated from pigs with respiratory clinical signs and determine their resistance to antibiotics at the same time. A total of 27 T. pyogenes strains were obtained from Jilin Province, and the nanH, nanP, cbpA, fimC, and fimE virulence genes were detected in 7 (25.9%), 14 (51.9%), 18 (66.7%), 8 (29.6%), and 16 (59.3%) isolates, respectively. All isolates were observed to harbor plo and fimA genes. However, 27 T. pyogenes strains tested negative for fimG gene. Antibiotic susceptibility tests revealed that the isolated strains had extensive drug resistance, all isolates were sensitive to fluoroquinolones and penicillins antibiotics, and high levels of resistance were found to gentamicin (77.8%), amikacin (74.1%), erythromycin (85.2%), and azithromycin (85.2%). These results highlights the need for prudent use of specific antimicrobial agents in veterinary clinical treatment.

Background: The use of direct oral anticoagulant (DOAC) off-label doses in atrial fibrillation (AF) patients may result in poor clinical outcomes. However, the true prevalence remains scarce. This study aims at estimating the prevalence of DOAC off-label doses in AF patients.Methods: Databases of MEDLINE, EMBASE, and COCHRANE were searched from inception through February 2020 for real-world studies that reported the off-label definition and prevalence data of AF patients using DOACs. The primacy outcomes were the overall prevalence of DOAC off-label doses and the corresponding underdose and overdose. The random-effects model was used for data synthesis. Variations on individual DOAC and different regions were examined by subgroup analyses.Results: A total of 23 studies involving 162,474 AF patients were finally included. The overall prevalence of DOAC off-label doses was 24% (95% CI, 19–28%), with 18% for dabigatran, 27% for rivaroxaban, 24% for apixaban, and 26% for edoxaban. The prevalence of underdosed DOACs was 20% (95% CI, 16–24%) with significant difference among individual anticoagulants (13% for dabigatran, 22% for rivaroxaban, 22% for apixaban, and 18% for edoxaban; Pinteraction=0.02). The prevalence of overdosed DOACs was 5% (95% CI, 3–7%), with the lowest prevalence observed in apixaban (2%). Subgroup analyses by regions demonstrated that the prevalence of DOAC off-label doses was higher in Asia (32%) than in North America (14%) and in Europe (22%), with underdose being predominant. Regardless of different regions, the prevalence of overdose was relatively low (4–6%).Conclusion: This study provides an estimation of DOAC off-label doses in the real-world setting. The prevalence rate of DOAC off-label doses in AF patients was relatively high, with underdose being predominant. Clinicians in Asia preferred to prescribe underdose of DOACs to AF patients. More evidence about the appropriateness of DOAC off-label doses in AF patients is urgently needed. Education programs concerning the appropriate prescription of DOACs within the drug labels and accepted guidelines are necessary to DOAC prescribers to ensure the safety and effectiveness of anticoagulation therapy for patients with AF.

Background: The impact of concomitant impairments of left and right ventricular (LV and RV) strain on the long-term prognosis of acute ST-elevation myocardial infarction (STEMI) is not clear.Methods: We analyzed CMR images and followed up 420 first STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). These patients received timely primary percutaneous coronary intervention (PCI) within 12 h and CMR examination within 1 week (median, 5 days; range, 2–7 days) after infarction. Global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of both ventricles were measured based on CMR cine images. Conventional CMR indexes were also assessed. Primary clinical outcome was composite major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, re-hospitalization for heart failure and stroke. In addition, CMR data from 40 people without apparent heart disease were used as control group.Results: Compared to controls, both LV and RV strains were remarkably reduced in STEMI patients. During follow-up (median: 52 months, interquartile range: 29–68 months), 80 patients experienced major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, heart failure, and stroke. LV-GCS > −11.20% was an independent predictor of MACCEs (P < 0.001). RV-GRS was the only RV strain index that could effectively predict the risk of MACCEs (AUC = 0.604, 95% CI [0.533, 0.674], P = 0.004). Patient with RV-GRS ≤ 38.79% experienced more MACCEs than those with preserved RV-GRS (log rank P < 0.001). Moreover, patients with the concomitant decrease of LV-GCS and RV-GRS were more likely to experience MACCEs than patients with decreased LV-GCS alone (log rank P = 0.010). RV-GRS was incremental to LV-GCS for the predictive power of MACCEs (continuous NRI: 0.327; 95% CI: 0.095–0.558; P = 0.006). Finally, tobacco use (P = 0.003), right coronary artery involvement (P = 0.002), and LV-GCS > −11.20% (P = 0.012) was correlated with lower RV-GRS.Conclusions: The concomitant decrease of LV and RV strain is associated with a worse long-term prognosis than impaired LV strain alone. Combination assessment of both LV and RV strain indexes could improve risk stratification of patients with STEMI.Trial Registration:ClinicalTrials.gov, NCT03768453. Registered 7 December 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03768453.

Aims: This retrospective study assessed the association between sulfonylureas use and infarct size in patients with type 2 diabetes (T2DM) and ST-segment elevation myocardial infarction (STEMI) by myocardial enzymology indexes and cardiac magnetic resonance (CMR) imaging.Methods: Patients presenting STEMI between July 2013 and August 2019 were included in a retrospective database at our institution. Antidiabetic agents used before STEMI were recorded. Patients with maximum recorded troponin I (max cTNI) and creatine phosphokinase isoenzyme (CK-MB) within the first 72 h of chest pain onset were selected. Infarct size was quantified by CMR imaging, and cardiovascular outcomes were also obtained at 30 days and 6 months follow-up. Multivariable regression models explored potential risk factors associated with infarct size and clinical outcomes.Results: A total of 254 T2DM and STEMI patients were included, with 101 sulfonylurea users and 153 non-users. Sulfonylureas users were not associated with higher max cTnI and max CK-MB compared to non-users. Among 65 CMR patients, no significant differences in infarct size were detected between sulfonylureas users and non-users. Whereas, the incidence of microvascular obstruction (MVO) was higher in patients receiving sulfonylureas than those taking non-sulfonylureas (88.0 vs. 62.5%, p = 0.023). No higher cardiovascular events of sulfonylureas users vs. non-users were observed, except for heart failure events (24.0 vs. 2.5% at 30 days, p = 0.011; 28.0 vs. 2.5% at 6 months, p = 0.004). Multivariable regression analyses verified that sulfonylureas users increased the risks of MVO.Conclusions: Sulfonylureas use did not associate with larger infarct size in patients with T2DM and STEMI. A potentially higher incidence of MVO in sulfonylurea users was found. Notably, since most patients presented after a relatively long period of ischemia and glibenclamide was not used by the included patients in this observational study, the results of this study should not be extrapolated to clinical settings with short periods of ischemia or to patients using glibenclamide.

Background: Catheter ablation for parahisian ventricular arrhythmias (PHVA) is technically challenging and associated with risks of atrioventricular block (AVB). We developed a stepwise approach to improve the efficacy and safety of PHVA ablation. Methods: Forty-three patients (26 males; average age 65.8 ±10.4 years) with PHVAs were enrolled. A stepwise approach comprising differential electrocardiogram, sequential mapping and ablation beneath/above the septal leaflet of the tricuspid valve (SLTV) and at the neighboring/contralateral regions (the aortic root and sub-aortic valve region) was applied for PHVA. The effectiveness and safety of the stepwise approach was evaluated at the end of one year’s follow-up. Results: Sequential ablation beneath the SLTV (B-SLTV) succeeded in 24 (66.7 %) of 36 with right PHVA and ablation above the SLTV succeeded in 6 of the remaining12 with failed B-SLTV ablation. Target-His bundle (HB) distance > 4.5 mm significantly predicted successful right PHVA ablation (OR 1.703; 95% CI 1.084-2.676, P=0.02). “Seeming” right PHVA by electrocardiogram in 4 and apparent left PHVA in 3 was successfully ablated at the sub-aortic parahisian region. At the end of one year’s follow-up, 27 (75%) of 36 patients with right PHVA and 6 (85.7%) of 7 patients with left PHVA were free of PHVA recurrence off anti-arrhythmic drugs. The total success rate was 76.7% by using the stepwise approach for PHVA. One patient with A-SLTV ablation underwent pacemaker implantation due to complete AVB. Conclusions: The stepwise approach was effective and safe for treating PHVA. The target-HB distance was a significant predictor for right PHVA ablation

Vitamin D metabolites are fat-soluble vitamins that regulate broad spectrum of physiological and pathological processes. Accurate and high-throughput methods for the detection of vitamin D metabolites are essential to elucidate body functions. In this study, a sensitive and high throughput ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method was proposed for the accurate quantification of six vitamin D metabolites, including vitamin D2, vitamin D3, 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and 1,25-dihydroxyvitamin D3. Through the optimization of chromatographic and mass spectrometric conditions, only 20 μL serum or plasma could satisfy the quantification of six vitamin D metabolites. The limit of detection (LOD) was determined to be 0.02-0.05 pg mL-1. The validation method was carried out following the International Council for Harmonization (ICH) guidelines. All quantification performances, including linearity, accuracy, precision, extraction recovery and matrix effect, were investigated and were satisfactory for the accurate detection of vitamin D metabolites. A disease of the liver or kidney, the main organs for vitamin D metabolism, could lead to abnormal levels of vitamin D. Here, the established UHPLC-MS/MS method was further used for determination of vitamin D levels in plasma samples of patients after liver or kidney transplantation. Thirty-three liver transplant recipients (LTRs) and 63 kidney transplant recipients (KTRs) were included in this study. Vitamin D deficiency or insufficiency is common in KTRs and LTRs, with a prevalence of more than 99%.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become global pandemic and resulted in considerable morbidity and mortality since December 2019. Information on the incidence of myocardial injury remains scarce. METHODS: English-language databases (PubMed, Embase, Cochrane), Chinese-language databases (CNKI, VIP, WANFANG), and preprint platform were searched to identify studies that reported the myocardial injury data in COVID-19 patients. Random-effects meta-analyses were used to derive the pooled incidence and relative risks (RRs) of myocardial injury. Variations by disease severity were examined by subgroup analyses. Sensitivity analyses were performed to strengthen the results. Meta-regression was applied to explore the risk factors associated with myocardial injury. RESULTS: A total of 53 studies involving 7,679 patients were included. The pooled incidence of myocardial injury was 21% [95% confidence interval (CI), 17–25%; I(2), 96.5%]. The highest incidence of myocardial injury was found in non-survivors (66%; 95 CI%, 54–78%; I(2), 85.7%), followed by severe patients (43%; 95 CI%, 33–53%; I(2), 93.0%) and non-severe patients (11%; 95 CI%, 7–15%; I(2), 95.2%). Higher risk of myocardial injury was detected in severe patients than non-severe patients (RR, 5.74; 95% CI, 3.74–8.79; I(2), 86.8%). All the sensitivity analyses confirmed the robustness of primacy results. CONCLUSIONS: This meta-analysis showed that myocardial injury occurred in 21% of COVID-19 patients. An elevated rate was observed in non-survivors (66%) and severe patients (43%). Severe patients had a 4.74-fold increase in the risk of myocardial injury than non-severe patients. Aggressive strategy may be considered for COVID-19 patients at high risk of myocardial injury.

Protecting soil from Pb contamination has been a programme for a long time in China. However, research on lead pollution in wetlands remains rare. To understand the characteristics of Pb pollution in Beijing and the sources of contamination of different soil samples in wetlands, we collected samples during all four seasons from two soil horizons and analyzed their Pb concentrations and Pb isotope ratios. The average concentrations of Pb varied from 65.44 mg/kg in spring to 106.11 mg/kg in winter. Concentrations in autumn were significantly lower than those in spring and summer and were notably different between A and B Horizons (59.42 and 71.47 mg/kg, respectively). The Pb isotopic compositions show that Pb pollution results from a mixing of geogenic and anthropogenic materials. The ratios of

Background: Emerging publication of high-quality observational studies (OSs) fuel reassessment of treatment effect of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF). Methods: The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched (through July 1, 2019) for eligible OSs and randomized controlled trials (RCTs) that reported effectiveness outcomes [stroke or systemic embolism (SE)] or safety outcomes [intracranial haemorrhage (ICH), major bleeding, gastrointestinal bleeding (GIB), myocardial infarction (MI), and all-cause mortality] for DOACs and vitamin-K antagonists (VKAs) in elderly AF patients. A random-effects model was applied to separately calculate adjusted hazard ratios (HRs) for OSs and relative risks (RRs) for RCTs, and interaction analyses and the ratio of HR (RHR) were used to assess the comparability between OSs and RCTs. Results: A total of 32 studies involving 547,419 patients were included. No significant difference on treatment effect estimates was found between 27 OSs and 5 RCTs (Pinteraction>0.05 for each and all 95% confidence interval [CI] of RHR crossed 1.0). Compared with VKAs, DOACs significantly reduced risk for stroke/SE (OSs, HR: 0.87, 95% CI: 0.81-0.94; RCT, RR: 0.82, 95% CI: 0.67-0.96) and ICH (OSs: 0.47 [0.37-0.57]; RCTs: 0.47 [0.31-0.63]), without increasing risk for GIB (OSs: 1.21 [0.98-1.43]; RCTs: 1.34 [0.91-1.77]) and all-cause mortality (OSs: 1.01 [0.92-1.11]; RCTs: 0.94 [0.87-1.00]). Among OSs, DOACs significantly decreased risk for major bleeding (0.87 [0.77-0.98]) and MI (0.89 [0.79-0.99]). Dabigatran, but not other DOACs, significantly increased risk for GIB (1.48 [1.23-1.72]). Conclusions: DOACs were demonstrated to be more effective and safer than VKAs in elderly AF patients. Whereas, dabigatran users had a 48% increase in risk for GIB.

Cr(VI) is a common wastewater pollutant. Various adsorbents including carbon-based materials are used for the removal of Cr(VI) owing to their high adsorption capacity. Chemical activation is an effective method to increase the specific surface area of adsorbents and, thus, further improve their adsorption capacity. However, research on the adsorption and removal of Cr(VI) from aqueous solutions by chemically activated carbon spheres is limited. Here, glucose and sodium dodecylbenzene sulfonate were used to produce carbon spheres (CSs) via hydrothermal synthesis. Activated carbon spheres (ACSs) were then derived using KOH. The adsorption of Cr(VI) in solution by CS and ACS was investigated through batch experiments. The results indicate that the specific surface area of the ACS was 1491.21 m2 g−1, which was much higher than that of the CS. The adsorption kinetics of the sorbent was consistent with the pseudo-second-order kinetic model and the adsorption isotherm followed the Langmuir model. This indicated that the adsorption process of the ACS with respect to Cr(VI) was mainly via single molecular layer adsorption and chemisorption. In a 200 mg L−1 Cr(VI) solution, the maximum amount of Cr(VI) adsorbed by the ACS was 230.15 mg g−1, and some of these adsorbed Cr(VI) were reduced to Cr(III). These results show that ACSs have strong potential for application in the removal of Cr(VI) from aqueous solutions.

Recently, new cationic antibacterial peptide OM19R has been designed with low minimum inhibitory concentration (MIC) values against some gram-negative bacteria, such as Escherichia coli, Salmonella, and Shigella. However, this hybrid peptide, like most antibacterial peptides, has low enzyme stability and short half-life, which, in turn, increases the drug's cost. In this study, an antibacterial peptide (OM19r-8) was obtained containing some D-Arg amino acids. The new preparations were carried out through the replacement of l -Arginine by d -Arginine and the addition of PEG chains. Firstly, eight OM19r series of antibacterial peptides were obtained by designing D-Arg. Then, a polyethylene glycol-modified product mPEG5-butyrALD-OM19r-8 (mPEG5-OM19r-8) was isolated and purified by reverse-phase high-performance liquid chromatography (RT-HPLC). The enzyme stability test showed that the resistance of antibacterial peptide OM19r-8 to protease degradation increased by 4-32-fold. Moreover, the Time-kill studies showed that the germicidal kinetics curves of mPEG5-OM19r-8 and OM19r-8 to Escherichia coli had a similar trend, thus suggesting that PEG modification has an acceptable effect on the activity of the original peptide. Furthermore, the elimination of half-life (28.09 ± 2.81min) of mPEG5-OM19r-8, and the area under the drug concentration-time curve (2686.48 ± 651.36min∗ug/ml) was significantly prolonged. The current study demonstrates an example that optimizes the AMP by utilizing L-to-D amino acid replacement and including PEG chains. These results provide useful data for the clinical application of the mPEG5-OM19r-8.

Background: Emerging evidence shows that coronavirus disease 2019 (COVID-19) is commonly complicated by coagulopathy, and venous thromboembolism (VTE) is considered to be a potential cause of unexplained death. Information on the incidence of VTE in COVID-19 patients, however, remains unclear.Method: English-language databases (PubMed, Embase, Cochrane), Chinese-language databases (CNKI, VIP, WANFANG), and preprint platforms were searched to identify studies with data of VTE occurrence in hospitalized COVID-19 patients. Pooled incidence and relative risks (RRs) of VTE were estimated by a random-effects model. Variations were examined based on clinical manifestations of VTE (pulmonary embolism-PE and deep vein thrombosis-DVT), disease severity (severe patients and non-severe patients), and rate of pharmacologic thromboprophylaxis (≥60 and

A previous study described a novel serine protease inhibitor 16 from Musca domestica (MDSPI16), which inhibited the elastase and chymotrypsin. It also exhibited a potential anti-inflammatory activity for acute lung injury (ALI), while its effects on ALI are yet to be elucidated. The present study aimed to investigate the effects and the underlying mechanisms of MDSPI16 on lipopolysaccharide (LPS)-challenged mice and bone marrow neutrophils. The ALI model based on the results of LPS-induced mice demonstrated that MDSPI16 markedly reduced the infiltration of inflammatory cells, protein exudation in lung tissues, and downregulated the level of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α). Furthermore, the LPS-stimulated mouse bone marrow neutrophils model was employed to determine the role of MDSPI16. The cytokine levels were quantified by both the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Consequently, the expression of IL-6, IL-1β, and TNF-α was found to be inhibited by MDSPI16 in a dose-dependent manner. Moreover, MDSPI16 also inhibited the mouse neutrophils nuclear factor-κB (NF-κB) signaling pathway, c-Jun N-terminal kinase (JNK) signaling pathway, ERK1/2 and AP-1 signaling pathway in addition to the expression of iNOS and COX-2 proteins, which in turn, might alleviate the release of pro-inflammatory cytokines during ALI. Therefore, MDSPI16 could be proposed as a potential and novel drug therapy for ALI.

Background Heart failure (HF) is associated with an increased incidence of thromboembolic events. Antithrombotic treatment could reduce the stroke risk, whereas increase the bleeding risk. Whether antithrombotic treatment should be a routine therapy for HF and sinus rhythm (SR) patients remains unanswered. Methods We systematically searched Medline, Embase, Cochrane Library databases, and ClinicalTrials.gov Website for randomized controlled trials (RCTs) studying antithrombotic therapy in HF and SR patients. The primary outcomes of efficacy and safety were defined as stroke and major bleeding, respectively. The network meta-analysis was conducted. The results were expressed as relative risks (RRs) with 95% confidence intervals (95% CIs), and pooled using a random-effects model. The surface under the cumulative ranking curves (SUCRA) was calculated and trade-off analysis of net clinical benefit (NCB) was estimated. Results Five studies totally involving 9390 patients were included. A significantly decreased risk of stroke was found for patients with HF and SR, when rivaroxaban was compared with placebo (RR: 0.67, 95%CI: 0.47–0.96) and warfarin was compared with antiplatelets (RR: 0.49, 95%CI: 0.33–0.73). Warfarin (RR: 7.96, 95%CI: 1.06–59.88) and rivaroxaban (RR: 1.65, 95%CI: 1.16–2.33) were associated with a significant increase in the risk of major bleeding when compared with placebo. Considering the ranking of each antithrombotic therapy for primary outcomes, warfarin (SUCRA: 78.2) emerged with the highest cumulative ranking probability for stroke, with rivaroxaban (SUCRA: 73.9) and antiplatelet agents (SUCRA: 19.6) ranked behind. In terms of major bleeding, rivaroxaban (SUCRA: 57.6) was the safer intervention compared with antiplatelet agents (SUCRA: 43.5) or warfarin (SUCRA: 2.9). No difference was observed considering all-cause death, MI and hospitalization of HF among all different antithrombotic regimens. Rivaroxaban was considered as a reasonably effective and the safe antithrombotic agent for HF and SR patients. Conclusions Rivaroxaban might the optimal antithrombotic regimen balancing stroke and major bleeding for HF patients with SR. The results might support the attempt to anticoagulation on HF and SR patients. However, further specialized designs of RCTs are necessary to draw a robust conclusion.

Aeromonas veronii is a major pathogenic bacterium in humans and animals. When it causes outbreaks, there are enormous economic losses to the aquaculture industry. An effective live attenuated vaccine strain, ΔhisJ, was obtained in our previous studies by gene knockout in Aeromonas veronii TH0426 using the suicide vector pRE112. Here, we evaluated whether the live attenuated vaccine ΔhisJ was suitable for prevention of Aeromonas veronii infection by injection and immersion in loaches. Compared with that of the TH0426 wild-type strain, the virulence of the live vaccine was significantly weakened. Vaccine safety assessment results also indicated that 1 × 107 CFU/mL live vaccine was safe and did not induce clinical symptoms or obvious pathological changes. Additionally, after challenging loaches with Aeromonas veronii TH0426, the relative percent survival of the IN3 injection group was 65.66%, and that of the IM group was 50.78%. Our data show that the live attenuated vaccine ΔhisJ can improve the immune protection rate of loaches. Furthermore, increased enzyme activity parameters (SOD, LZM, ACP, and AKP) in the skin mucus, increased enzyme activity parameters (SOD, LZM, ACP, AKP, and GPx) in the serum, increased specific IgM antibodies and cytokine IL-1β contents in the serum, and increased cytokine (IL-15, pIgR, IL-1β, and TNF-α) expression in the liver and spleen were observed. These data are the first to indicate that the live attenuated vaccine ΔhisJ is suitable for the development of a safe and effective vaccine against Aeromonas veronii infection in loach aquaculture.

AIM To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus (HCV) infection (OCI). METHODS One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection (CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system. RESULTS CXCL10 rs1439490 G/G was more prevalent in OCI patients (n = 93/103; 90.3%) than in CHC patients (n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients (192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peg-interferon treatment than CHC patients (P < 0.05) and serum CXCL10 decreased significantly (P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection (OR = 0.31, 95%CI: 0.15-0.66, P = 0.002). CONCLUSION CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.

The poor stability of antibacterial peptide to protease limits its clinical application. Among these limitations, trypsin mainly exists in digestive tract, which is an insurmountable obstacle to orally delivered peptides. OM19R is a random curly polyproline cationic antimicrobial peptide, which has high antibacterial activity against some gram-negative bacteria, but its stability against pancreatin is poor. According to the structure-activity relationship of OM19R, all cationic amino acid residues (l-arginine and l-lysine) at the trypsin cleavage sites were replaced with corresponding d-amino acid residues to obtain the designed peptide OM19D, which not only maintained its antibacterial activity but also enhanced the stability of trypsin. Proceeding high concentrations of trypsin and long-time (such as 10 mg/mL, 8 h) treatment, it still had high antibacterial activity (MIC = 16–32 µg/mL). In addition, OM19D also showed high stability to serum, plasma and other environmental factors. It is similar to its parent peptide in secondary structure and mechanism of action. Therefore, this strategy is beneficial to improve the protease stability of antibacterial peptides.

Purpose Blood-brain barrier (BBB) damage is closely related to various neurological disorders, including bacterial meningitis (BM). Determining a reliable strategy to prevent BBB damage in the context of infection would be highly desirable. In the present study, we investigated the implications of the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in moderating BBB damage. Methods In vitro BBB models were developed by co-culturing hCMEC/D3 cells with glioma cells, whereupon the glioma-exposed endothelial cells (GECs) were treated with a series of mimics, inhibitors, overexpression plasmids, and shRNAs for evaluating whether NEAT1, microRNA-135a (miR-135a) and hypoxia-inducible factor 1α (HIF1α) mediated BBB integrity and permeability. Furthermore, the in vivo biological function of NEAT1 was validated in a mouse model of BBB damage. Results NEAT1 and HIF1α were determined to be up-regulated, while miR-135a was under-expressed in GECs. As demonstrated by chromatin immunoprecipitation and dual-luciferase reporter assays, NEAT1 could bind to miR-135a, and HIF1α was confirmed as a target of miR-135a. Either overexpression of NEAT1 or depletion of miR-135a impaired the integrity and augmented the permeability of BBB. However, HIF1α silencing could reverse the BBB damage induced by NEAT1 overexpression or by inhibition of miR-135a. In vivo experiments substantiated that knockdown of NEAT1 could alleviate BBB damage in living mice. Conclusions Hence, NEAT1 knockdown prevents BBB disruption and exerts promise as a potential target for BM treatment.

// Ying-Chun Song 1, * , Gai-Xia Lu 1, * , Hong-Wei Zhang 2, * , Xiao-Ming Zhong 3, * , Xian-Ling Cong 4, * , Shao-Bo Xue 1, * , Rui Kong 1, * , Dan Li 1 , Zheng-Yan Chang 5 , Xiao-Feng Wang 6 , Yun-Jie Zhang 6 , Ran Sun 4 , Li Chai 1 , Ru-Ting Xie 5 , Ming-Xiang Cai 1 , Ming Sun 1 , Wei-Qing Mao 1 , Hui-Qiong Yang 5 , Yun-Chao Shao 6 , Su-Yun Fan 1 , Ting-Miao Wu 1 , Qing Xia 6 , Zhong-Wei Lv 1 , David A. Fu 6 and Yu-Shui Ma 1, 7 1 Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China 2 Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China 3 Department of Radiology, Jiangxi Provincial Tumor Hospital/Ganzhou City People’s Hospital, Nanchang 330029, China 4 Department of Biobank, China-Japan Unoin Hospital, Jilin University, Changchun 130033, China 5 Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China 6 Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China 7 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China * These authors have contributed equally to this work Correspondence to: Zhong-Wei Lv, email: shtjnmd@163.com David A. Fu, email: 061101021@fudan.edu.cn Yu-Shui Ma, email: mayushui2015@126.com Keywords: GBM, glioma, proteomics analysis, gene expression analysis, Bioinformatics Analysis Received: May 24, 2017 Accepted: August 26, 2017 Published: October 19, 2017 ABSTRACT Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples. A validation cohort included 529 GBM patients from The Cancer Genome Atlas datasets. We identified 36 molecules commonly changed at the level of the gene and protein, including up-regulated TGFBI and NES and down-regulated SNCA and HSPA12A. Single amino acid variant analysis identified 200 proteins with high mutation rates in GBM samples. We further identified 14 differentially expressed genes with high-level protein modification, among which NES and TNC showed differential expression at the protein level. Moreover, higher expression of NES and TNC mRNAs correlated with shorter overall survival, suggesting that these genes constitute potential biomarkers for GBM.

To determine the associations of self-reported sleep quality and duration with health-related quality of life (HRQOL) in older Chinese.We analyzed community-based cross-sectional data of 5,539 individuals aged 60 years and older in the Weitang Geriatric Disease Study. Information of sleep quality and duration were self-reported through participants' responses to predefined questions; HRQOL data were collected by using the European Quality of Life-5 Dimensions (EQ-5D). We estimated the associations of sleep quality and duration with the EQ-5D index and visual analog scale (VAS) scores using linear regression models. The associations between sleep quality and duration and EQ-5D-detected health problems were modeled using logistic regression.In multiple linear models adjusting sociodemographic factors, health conditions, and lifestyle habits, both EQ-5D index and VAS scores declined with deterioration of sleep quality. The coefficients for poor and intermediate sleep quality were -0.053 (95% confidence interval [CI]:-0.065, -0.042) and -0.022 (95% CI: -0.030, -0.013), respectively, in relation to EQ-5D index score. They were -5.2 (95% CI: -6.7, -2.4) and - 3.8 (95% CI: -4.9, -2.7) in modeling the EQ-5D VAS score. HRQOL declined as sleep duration decreased below 7.01 hours or exceeded 8.01 hours, though most of the associations did not reach statistical significance. In multiple logistic models, poor sleep quality was associated with problems of mobility, pain/discomfort, and anxiety/ depression; short sleep duration was associated with mobility problems.Poor sleep quality and extreme sleep durations appeared to be negatively associated with HRQOL in older Chinese adults.

Background In recent years, highly frequent swine respiratory diseases have been caused by extraintestinal pathogenic Escherichia coli (ExPEC) in China. Due to this increase in ExPECs, this bacterial pathogen has become a threat to the development of the Chinese swine industry. To investigate ExPEC pathogenesis, we isolated a strain (named SLPE) from lesioned porcine lungs from Changchun in China, reported the draft genome and performed comparative genomic analyses. Results Based on the gross post-mortem examination, bacterial isolation, animal regression test and 16S rRNA gene sequence analysis, the pathogenic bacteria was identified as an ExPEC. The SLPE draft genome was 4.9 Mb with a G + C content of 51.7%. The phylogenomic comparison indicated that the SLPE strain belongs to the B1 monophyletic phylogroups and that its closest relative is Avian Pathogenic Escherichia coli (APEC) O78. However, the distribution diagram of the pan-genome virulence genes demonstrated significant differences between SLPE and APEC078. We also identified a capsular polysaccharide synthesis gene cluster (CPS) in the SLPE strain genomes using blastp. Conclusions We isolated the ExPEC (SLPE) from swine lungs in China, performed the whole genome sequencing and compared the sequence with other Escherichia coli (E. coli). The comparative genomic analysis revealed several genes including several virulence factors that are ExPEC strain-specific, such as fimbrial adhesins (papG II), ireA, pgtP, hlyF, the pix gene cluster and fecR for their further study. We found a CPS in the SLPE strain genomes for the first time, and this CPS is closely related to the CPS from Klebsiella pneumoniae. Electronic supplementary material The online version of this article (doi:10.1186/s12917-017-1093-5) contains supplementary material, which is available to authorized users.

Previous studies have suggested that dysregulation of microRNA (miR) -124a is associated with various types of human cancer. However, there are few studies reporting the level of miR‑124a expression in non‑small cell lung cancer (NSCLC). The present study investigated the association between miR‑124a and NSCLC by analyzing the differential expression of miR‑124a in NSCLC using the GEO database, as well as subsequently performing reverse transcription‑quantitative polymerase chain reaction analysis on 160 NSCLC biopsies, 32 of which were paired with adjacent normal tissues. The results indicated that mir‑124a expression levels were decreased in NSCLC tumor biopsies compared with adjacent normal tissues. The overall survival (OS) in patients with a high expression of miR‑124a was prolonged relative to patients with low expression of miR‑124a. The expression levels of miR‑124a were associated with clinical characteristics, including lymph‑node metastasis, tumor differentiation, tumor node metastasis (TNM) stage and diameter. Frequently, lymph‑node metastasis, TNM stage, diameter and lack of chemotherapy have been associated with a worse prognosis in patients. In addition, the present study identified that high expression of miR‑124awith chemotherapy may increase OS. In conclusion, the current study demonstrated that miR‑124a was downregulated in NSCLC, and miR‑124a was a potential prognostic tumor biomarker response to chemotherapy.

Twenty-three isolates of Pasteurella multocida were tested for susceptibility to six aminoglycoside agents and screened by polymerase chain reaction for the presence of aminoglycoside resistance genes. In addition, mutations in the resistance-determining region of strains showing a high level of induced resistance to spectinomycin strains were examined. Susceptibility testing showed that all of the isolates were resistant to at least two types of aminoglycosides, and that the most effective antimicrobial was spectinomycin. The resistance genes aphA1, strB and aacA4 were present in all 23 isolates. In the three induced spectinomycin-resistant strains, a 9-bp deletion in rpsE that encodes ribosomal protein S5 was detected.

It has been estimated that nearly one-fifth post-percutaneous coronary intervention (PCI) patients treated with clopidogrel continued to have recurrent thrombotic events, which implied the limitation of "one-size-fits all" strategy for antiplatelet therapy.From July 2017 to April 2019, patients with acute coronary syndrome [ACS, including unstable angina (UA), non-ST segment elevation myocardial infraction (NSTEMI), and ST segment elevation myocardial infraction (STEMI)] or old myocardial infarction (OMI), or patients without coronary heart disease (non-CAD) were retrospectively enrolled in this study. For CAD patients undergoing PCI, standard dual antiplatelet therapy (100 mg aspirin and 75 mg clopidogrel) was prescribed. After administration of dual antiplatelet agents for at least 5 days, whole blood samples were collected and platelet function was tested using thrombelastography (TEG). Thrombin-induced platelet-fibrin clot strength (MAthrombin) and ADPinduced platelet-fibrin clot strength (MAADP) were measured to assess the hypercoagulability and antiplatelet effects.A total of 571 patients, including 479 ACS patients, 21 OMI patients and 71 non-CAD patients were enrolled. Highest level of MAthrombin was detected in STEMI patients, while lowest MAthrombin level was observed in non-CAD patients (P10.05 for OMI vs. non-CAD; P20.001 for ACS vs. non-CAD; P30.05 among ACS). Higher MAADP was also observed in STEMI and NSTEMI patients compared with UA patients (P0.001). When MAADP was divided into trisections (MAADP31; 31-47;47 mm), a considerable portion of 41.8% ACS patients were in the first trisection (MAADP31 mm), containing 50.4% of UA patients, 35.7% of NSTEMI patients and 26.5% of STEMI patients, with significant difference being observed between UA patients and other ACS patients (P0.05 for NSTEMI vs. UA; P0.001 for STEMI vs. UA). Meanwhile, 27.6% of NSTEMI and 31.0% of STEMI patients were in the third trisection (MAADP47 mm), which was significantly higher than that of UA patients (12.7%) (P0.001 for NSTEMI or STEMI vs. UA).Considering various degrees of hypercoagulability and antiplatelet effects of clopidogrel among OMI and ACS patients post-PCI. More attention should be paid to personalized antiplatelet therapy according to individual's effects of P2Y12 receptor inhibitors.

Bacterial enteritis is the most important disease in lamb for breeding greatly affects the growth of animals. Changes in the community of intestinal flora can cause the disorder of the colonic environment induced diarrhea. This study aimed to investigate the relationship between the incidence of bacterial enteritis and the number of intestinal microbiome, then the prevalence of drug-resistant genes was detected. Fecal samples were collected at five fattening sheep farms with different incidence of bacterial enteritis, pathogenic bacteria were isolated and identified, drug sensitivity tests were performed. Then, changes in number and structure of intestinal flora were compared by 16S rDNA V3-V4 region high-throughput sequencing, and the ARGs were detected using high-throughput real-time PCR. Our results revealed that the microbial communities were positively correlated with the incidence of bacterial enteritis in different farms. Bacterial communities were higher in YJ (with highest incidence of diarrhea) than any other farms. However, the ARGs seemed not to be more affected by the incidence of bacterial enteritis, but one of the significant findings to emerge from this study is that MCR-1 and NDM are detected in manure. This study has provided an insight of the changes occurring in intestinal flora and AGRs in fattening sheep farms with diverse incidence of bacterial enteritis.

M. avium subsp. paratuberculosis (MAP) is the causative pathogen of Johne&rsquo, s disease, a chronic granulomatous enteritis that principally affects ruminants and can survive, proliferate and disseminate in macrophages. MicroRNAs (miRNAs) are important regulators of gene expression and can impact the processes of cells. To investigate the role of miRNAs in monocyte-derived macrophages (MDMs) during MAP infection, we used high-throughput sequencing technology to analyze small RNA libraries of MAP-infected and control MDMs. The results showed that a total of 21 miRNAs were differentially expressed in MDMs after MAP infection, and 8864 target genes were predicted. A functional analysis showed that the target genes were mainly involved in the MAPK signaling pathway, Toll-like receptor signaling pathway, NF-kappa B signaling pathway and apoptosis. In addition, using a dual-luciferase reporter assay, flow cytometry, and a small interfering (si)RNA knockdown assay, the role of miR-150 in regulating macrophage apoptosis by targeting the programmed cell death protein-4 (PDCD4) was demonstrated. These results provide an experimental basis to reveal the regulatory mechanism of MAP infection and suggest the potential of miRNAs as biomarkers for the diagnosis of Johne&rsquo, s disease in bovines.

Eugenol, the major active essential oil component of clove, was reported to possess QS (quorum sensing) inhibitory activity. A previous study found that eugenol could bind to quorum sensing receptors of Pseudomonas aeruginosa and down-regulate the expression of Streptococcus mutans virulence genes at sub-MIC (minimum inhibitory concentration) without affecting the bacterial growth. However, the alterations of QS signal molecules at transcription levels was not well understood. To better understand interactions of Klebsiella pneumoniae in response to eugenol and explore molecular regulations, transcriptome sequencing was performed. A total of 5779 differentially expressed genes (DEGs) enriched in a variety of biological processes and pathways were identified. The transcriptional data was validated by qPCR and the results showed that the expression profiles of 4 major genes involved in autoinducers-2 (AI-2) synthesis, including luxS, pfs, and lsrK were consistent with transcriptome analysis except for lsrR, a transcriptional repressor gene of lsr operon, which may repress the expression of following genes responsible for AI-2 signal transmission in vivo. In vitro AI-2 synthesis assay also revealed that eugenol could inhibit AI-2 generation. The results of our study offer insights into the mechanisms of QS inhibitory activity and K. pneumoniae AI-2 alterations after eugenol treatment.

The effect of glucagon-like peptide-1 (GLP-1) treatment in patients with type 2 diabetes mellitus (T2DM) remains controversial. The purpose of this study was to compare the effect of GLP-1 and placebo/conventional antidiabetic agents on cardiovascular risk in T2DM patients. PubMed, EmBase and the Cochrane Library were searched to identify its eligible studies as well as manual searches for the reliability of this study. All eligible trials were performed in T2DM patients who received GLP-1 therapy or placebo/conventional antidiabetic agents. The reported outcomes included major cardiovascular events (MACE), and total mortality. Of 490 identified studies, we included 13 trials reporting data on 11,943 T2DM patients. Overall, the pooled results suggested that GLP-1 therapy has no or little effect on MACE (RR: 0.99; 95% CI: 0.88-1.12; P=0.872) and total mortality (RR: 0.90; 95% CI: 0.70-1.15; P=0.399). Furthermore, sensitivity analysis indicated that GLP-1 was associated with lower incidence of total mortality (RR: 0.28; 95% CI: 0.08-0.93; P=0.037). We concluded that GLP-1 therapy was not associated with MACE and total mortality compared with placebo or antidiabetic agents.

Insect-derived serine protease inhibitors (serpins) exhibit multiple inhibitory activities, but so far, no functional roles for serpins of Musca domestica have been identified. Here, the functional features of M. domestica serine protease inhibitor (MDSPI16) were characterized. Hundred forty seven differentially expressed genes including the MDSPI16 gene were screened by constructing the subtractive cDNA library. The 1154-bp full-length MDSPI16 gene was cloned, and the recombinant MDSPI16 serpin protein was expressed as a 42.6 kDa protein in an Escherichia coli expression system. The recombinant MDSPI16 protein was purified using Ni–NTA affinity chromatography, and the inhibitory activity of MDSPI16 was assessed. MDSPI16 did not inhibit trypsin, papain, or proteinase K but strongly inhibited elastase (Ki = 2.8 nM) and chymotrypsin (Ki = 28 nM). The inhibitory activity of MDSPI16 remained stable over from 37 to 100 °C and from pH 2 to 12. The MDSPI16 exhibited inhibitory activity against elastase and chymotrypsin and the inhibitory activity remained stable.

Quantitative modification of TIMI myocardial perfusion grade (TMPG) by the method of frame counting may improve its sensitivity and the false negative rate for post-reperfusion microvascular dysfunction (MVD) in ST segment-elevated myocardial infarction (STEMI) patients.The durations of contrast-washout from infarction area of 139 patients were measured by counting the cine-frame numbers between the appearance and disappearance of myocardial blush. The achieved new index, TMP Frame Counting (TMP-FC) was referenced by cardiac magnetic resonance, by which MVD was defined as microvascular obstruction on gadolinium late-enhancement imaging.Median TMP-FC differed significantly between patients with and without MVD (126 frames, IQR 105-160 vs. 86 frames, IQR 75-100, p0.001). By receiver-operating characteristic analysis, the cutoff of TMP-FC at ≥ 95.5 frames represented an independent predictor of MVD (OR=11.61, p0.001). TMP-FC had similar specificity (75%) and positive predictive value (88%), but significantly improved sensitivity (85.3%) and negative predictive value (70.2%) for MVD compared with TMPG (88.6%, 86.5%, 33.7% and 38.2%, respectively) and other traditional angiographic assessments, leading to a better overall accuracy (area under the curve: 0.801 compared with 0.612 from TMPG, p0.001) for the evaluation of microvascular patency. TMP-FC was positively correlated with MVD extent (r=0.5, p0.001). Abnormal TMP-FC was associated with larger infarction size (28.67 ± 13.72% vs. 16.51 ± 10.68% of left ventricular mass, p0.001) and lower LVEF (49.37 ± 11.06% vs. 56.84 ± 9.72%, p0.001).Frame counting can improve the accuracy of TMPG for MVD. Moreover, TMP-FC is correlated with the degree of MVD and cardiac detriments, which is useful for risk stratification.

Background Left ventricular thrombus (LVT), a common complication of acute ST-segment elevation myocardial infarction (STEMI), is associated with increased risk of systemic embolism and high mortality. Current STEMI guidelines recommend adding anticoagulant therapy to dual antiplatelet therapy (DAPT) if early-formulated LVT were detected, for which vitamin K antagonist (VKA) is the standard anticoagulant agent. The role of non-VKA oral anticoagulants (NOACs) in this scenario is uncertain. Methods The EARLY-MYO-LVT study will be a prospective, multi-center and randomized trial designed to investigate the efficacy and safety of rivaroxaban versus warfarin in the treatment of post-STEMI LVT. It will enroll 280 patients with STEMI who have developed LVT within the first month of symptom onset. They will be randomized at 1:1 ratio into the group of rivaroxaban 15 mg daily or VKA treatment (with targeted INR 2-2.5) on the basis of standard DAPT (100 mg daily aspirin plus 75 mg daily clopidogrel) for 3-6 months. The primary efficacy endpoint will be the probability of LVT resolution after 3-month triple therapy, and the principal safety outcome will be the incidence of major bleeding events during the treatment. Discussion The described study will systemically assess the efficacy and safety of NOACs-based anticoagulant therapy in the treatment of LVT subsequent to STEMI. Trial registration The EARLY-MYO-LVT trial (Clinical trial number: NCT03764241).