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Abstract Background The impairment of endothelial function represents a key pathophysiological mechanism in the development of sepsis. This research aimed to evaluate the prognostic significance of angiopoietin-2 (Ang-2), an endothelial biomarker, in predicting mortality in sepsis patients. Methods Chinese and English studies were systematically retrieved in PubMed, Cochrane Library, Embase, WanFang, CNKI, CQVIP, and CBM databases up to July 16, 2023. We conducted a study selection established upon predefined inclusion and exclusion criteria and used the Newcastle-Ottawa scale (NOS) to assess its quality. We extracted available data from the included studies for data analysis. Results The final inclusion comprised 33 studies with 4703 participants. According to the NOS, one study was of medium quality, while the rest were of high quality. In comparison to survivors, the levels of Ang-2 in non-survivors were markedly elevated [standardized mean difference (SMD) = 1.08, 95% confidence intervals (CI) 0.68–1.49, P

Abstract Background and aims To our knowledge, no previously reported clinical data of a coronary artery fistula forming a pseudoaneurysm and presenting as a anterior chest wall lump. We reported a rare case of Coronary pseudoaneurysm with a superficial mass and accompanying Brucella infection. The patient was successfully treated with surgery. Materials and methods The patient case data was extracted from hospital records. Results A 64-year-old male presented with a history of paroxysmal left-sided chest pain and painful anterior chest wall lump. Coronary computed tomography (CT) angiography revealed the RCA pseudoaneurysm that showed a peripherally calcified soft-tissue mass in the anterior mediastinum and communicated with the chest wall lump through intercostal spaces. The patient underwent the resection of chest lump and RCA pseudoaneurysm under cardiopulmonary bypass, along with a combined antimicrobial therapy. The patient was discharged successfully after the surgery. Discussion and conclusion We report this rare case and highlight the possible origin of the anterior mediastinal mass and anterior chest wall lump as a pseudoaneurysm formed by a coronary artery fistula.

Abstract Background Disseminated intravascular coagulation (DIC) occurs in 30–50% of septic patients and contributes to high mortality in the intensive care unit (ICU). However, there are few proven interventions for coagulation disorder management in sepsis. Experimental and clinical data have demonstrated that sepsis could benefit from unfractionated heparin (UFH) treatment. To date, there are no large multicenter trials to determine the safety and efficacy of UFH in septic patients with suspected DIC. Methods A multicenter, double-blinded, placebo-controlled randomized trial is designed to recruit 600 patients who met sepsis 3.0 criteria and suspected DIC. Participants will be randomized (1:1) to receive UFH or saline via continuous intravenous administration for 7 days within 6 h of enrolment. The primary outcome is ICU mortality. The secondary outcome includes 28-day all-cause mortality, the improvement of Sequential Organ Failure Assessment scores, and the incidence of major hemorrhage. Investigators, participants, and statisticians will be blinded to the allocation. Discussion The HepSIC trial is to evaluate the efficacy and safety of UFH on sepsis-related DIC across different areas of China. The small dosage of UFH administration would offer a new potential approach for treating sepsis-related coagulation disorders. Ethics and dissemination Ethical approval was granted by all the ethics committees of 20 participant centers. Results will be disseminated via peer-reviewed publications and presented at conferences. Trial registration ClinicalTrials.gov NCT02654561. Registered on 13 January 2016.

Abstract Current guidelines give priority to surgical treatment of carotid artery stenosis (CAS) before coronary artery bypass grafting (CABG), especially in symptomatic patients. Carotid artery stenting is an alternative treatment for narrowing of the carotid arteries. This study sought to demonstrate the role of severe CAS in predicting stroke after CABG and assess the efficacy of carotid artery stenting in preventing postoperative stroke in a Chinese cohort. From 2015 to 2021, 1799 consecutive patients undergoing isolated CABG surgery were retrospectively recruited in a Chinese cohort. The predictive value of severe CAS in postoperative stroke and carotid stenting in preventing postoperative stroke was statistically analyzed. The incidence of postoperative stroke was 1.67%. The incidence of CAS with stenosis ≥ 50% and ≥ 70% was 19.2% and 6.9%. After propensity matching, the incidence of stroke was 8.0% in the severe CAS group and 0% in the non-severe CAS group. We successfully established an optimal predictive nomogram for predicting severe CAS in patients undergoing CABG. Carotid artery stenting was found ineffective in preventing postoperative stroke. The present study provides the incidence of CAS and postoperative stroke in a Chinese cohort, identifies severe CAS as an independent risk factor for postoperative stroke after CABG, constructs a nomogram predicting the incidence of severe CAS, and evaluates the effectiveness of carotid artery stenting in preventing postoperative stroke after CABG.

ABSTRACT: Egg weight (EW) and age at first egg (AFE) are economically important traits in breeder chicken production. The genetic basis of these traits, however, is far from understood, especially for broiler breeders. In this study, genetic parameter estimation, genome-wide association analysis, meta-analysis, and selective sweep analysis were carried out to identify genetic loci associated with EW and AFE in 6,842 broiler breeders. The study found that the heritability of EW ranged from 0.42 to 0.44, while the heritability of AFE was estimated at 0.33 in the maternal line. Meta-analysis and selective sweep analysis identified two colocalized regions on GGA4 that significantly influenced EW at 32 wk (EW32W) and at 43 wk (EW43W) with both paternal and maternal lines. The genes AR, YIPF6, and STARD8 were located within the significant region (GGA4: 366.86-575.50 kb), potentially affecting EW through the regulation of follicle development, cell proliferation, and lipid transfer etc. The promising genes LCORL and NCAPG were positioned within the significant region (GGA4:75.35-75.42 Mb), potentially influencing EW through pleiotropic effects on growth and development. Additionally, 3 significant regions were associated with AFE on chromosomes GGA7, GGA19, and GGA27. All of these factors affected the AFE by influencing ovarian development. In our study, the genomic information from both paternal and maternal lines was used to identify genetic regions associated with EW and AFE. Two genomic regions and eight genes were identified as the most likely candidates affecting EW and AFE. These findings contribute to a better understanding of the genetic basis of egg production traits in broiler breeders and provide new insights into future technology development.

Mycoplasma pneumoniae (M. pneumoniae) is a well-recognized pathogen primarily associated with respiratory tract infections. However, in rare instances, it can lead to extrapulmonary manifestations, including myocarditis. We present a case of a 15-year-old male who developed fulminant myocarditis, cardiogenic shock, and cardiac electrical storm attributed to M. pneumoniae infection. He underwent a combination of intra-aortic balloon pump (IABP) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiac support, ultimately surviving despite the intracardiac thrombus formation and embolic stroke. Following comprehensive treatment and rehabilitation, he was discharged in stable condition. This case underscores the importance of considering atypical pathogens as potential etiological factors in patients presenting with cardiac complications, especially in the adolescents. It also emphasizes the need for clinical vigilance and effective support for potential cardiac complications arising from M. pneumoniae infection.

Background: Streptococcus suis (S. suis) is a Gram-positive bacterium that causes substantial disease in pigs. S. suis is also an emerging zoonoses in humans, primarily in Asia, through the consumption of undercooked pork and the handling of infected pig meat as well as carcasses. The complexity of S. suis epidemiology, characterized by the presence of multiple bacterial serotypes and strains with diverse sequence types, identifies a critical need for a universal vaccine with the ability to confer cross-protective immunity. Highly conserved immunogenic proteins are generally considered good candidate antigens for subunit universal vaccines. Methods: In this study, the cross-protection of the sugar ABC transporter substrate-binding protein (S-ABC), a surface-associated immunogenic protein of S. suis, was examined in mice for evaluation as a universal vaccine candidate. Results: S-ABC was shown to be highly conserved, with 97% amino acid sequence identity across 31 S. suis strains deposited in GenBank. Recombinantly expressed S-ABC (rS-ABC) was recognized via rabbit sera specific to S. suis serotype 2. The immunization of mice with rS-ABC induced antigen-specific antibody responses, as well as IFN-γ and IL-4, in multiple organs, including the lungs. rS-ABC immunization conferred high (87.5% and 100%) protection against challenges with S. suis serotypes 2 and 9, demonstrating high cross-protection against these serotypes. Protection, albeit lower (50%), was also observed in mice challenged with S. suis serotype 7. Conclusions: These data identify S-ABC as a promising antigenic target within a universal subunit vaccine against S. suis.

Japanese encephalitis (JE) is a zoonotic ailment from the Japanese encephalitis virus (JEV). JEV belongs to the flavivirus genus and is categorized into a solitary serotype consisting of five genetically diverse genotypes (I, II, III, IV, and V). The JEV genotype III (GIII) was the prevailing strain responsible for multiple outbreaks in countries endemic to JEV until 1990. In recent years, significant improvements have occurred in the epidemiology of JE, encompassing the geographical expansion of the epidemic zone and the displacement of prevailing genotypes. The dominant genotype of the JEV has undergone a progressive shift from GIII to GI due to variations in its adaptability within avian populations. From 2021 to 2022, Australia encountered an epidemic of viral encephalitis resulting from infection with the GIV JEV pathogen. The current human viral encephalitis caused by GIV JEV is the initial outbreak since its initial discovery in Indonesia during the late 1970s. Furthermore, following a time frame of 50 years, the detection and isolation of GV JEV have been reported in Culex mosquitoes across China and South Korea. Evidence suggests that the prevalence of GIV and GV JEV epidemic regions may be on the rise, posing a significant threat to public safety and the sustainable growth of animal husbandry. The global approach to preventing and managing JE predominantly revolves around utilizing the GIII strain vaccine for vaccination purposes. Nevertheless, research has demonstrated that the antibodies generated by the GIII strain vaccine exhibit limited capacity to neutralize the GI and GV strains. Consequently, these antibodies cannot protect against JEV challenge caused by animal GI and GV strains. The limited cross-protective and neutralizing effects observed between various genotypes may be attributed to the low homology of the E protein with other genotypes. In addition, due to the GIV JEV outbreak in Australia, further experiments are needed to evaluate the protective efficiency of the current GIII based JE vaccine against GIV JEV. The alteration of the prevailing genotype of JEV and the subsequent enlargement of the geographical extent of the epidemic have presented novel obstacles in JE prevention and control. This paper examines the emerging features of the JE epidemic in recent years and the associated problems concerning prevention and control.

ABSTRACT: The weight of breast muscle (WBM) is a highly monitored indicator in broiler breeding that can be obtained after slaughtering. Currently, due to the lack of accurate in vivo phenotypes for both genomic and phenotypic selection, genetic gains in WBM fall short of initial expectations. In this study, 1,006 market-age (42 d) broilers from 3 generations over 2 yr were randomly selected, and the breast width (BW), fossil bone length (FBL), breast muscle thickness (BMT), and live weight (LW) were measured exactly in vivo. Eight models, including multiple linear regression (MLR), ridge regression (RR), least absolute shrinkage and selection operator (LASSO), and elastic net (EN), were fitted to explore the best regression relationships between breast muscle weight and these indicators. Support vector machine (SVM) methods with both linear kernels and radial kernels were used to fit the models, while 2 decision tree-based machine learning algorithms, random forest (RF), and extreme gradient boosting (XGBoost), were used to establish the prediction model. The predictive effects of different combinations of independent variables were compared, leading to the conclusion that the EN model achieves the best predictive power when all 4 live features are used as inputs and is slightly better than the other models (R2 = 0.7696). This method could be applied in practical production and breeding work, leading to substantial cost savings and enhancements in the breeding process.

Here, we report an unusual case of left atrial myxoma presented with morphology of cavernous hemangioma supplied by the right coronary artery. Surgical resection of the left atrium myxoma was performed, and the patient experienced an uneventful recovery during hospitalization.

Abstract Background Less is known about the risk factors for acute respiratory distress syndrome (ARDS) in sepsis patients diagnosed according to sepsis 3.0 criteria. Moreover, the risk factors for ARDS severity remain unclear. Methods We retrospectively collected the characteristics of sepsis patients from the intensive care unit of the First Affiliated Hospital of China Medical University from January 2017 to September 2018. Logistic regression was used in determining the risk factors. Results 529 patients with sepsis were enrolled and 179 developed ARDS. The most common infection sites were acute abdominal infection (n = 304) and pneumonia (n = 117). Multivariate analysis showed that patients with pancreatitis with local infection (odds ratio [OR], 3.601; 95% confidence interval [CI], 1.429–9.073, P = 0.007), pneumonia (OR 3.486; 95% CI 1.890–6.430, P

Abstract Background This study was performed to develop and validate machine learning models for early detection of ventilator-associated pneumonia (VAP) 24 h before diagnosis, so that VAP patients can receive early intervention and reduce the occurrence of complications. Patients and methods This study was based on the MIMIC-III dataset, which was a retrospective cohort. The random forest algorithm was applied to construct a base classifier, and the area under the receiver operating characteristic curve (AUC), sensitivity and specificity of the prediction model were evaluated. Furthermore, We also compare the performance of Clinical Pulmonary Infection Score (CPIS)-based model (threshold value ≥ 3) using the same training and test data sets. Results In total, 38,515 ventilation sessions occurred in 61,532 ICU admissions. VAP occurred in 212 of these sessions. We incorporated 42 VAP risk factors at admission and routinely measured the vital characteristics and laboratory results. Five-fold cross-validation was performed to evaluate the model performance, and the model achieved an AUC of 84% in the validation, 74% sensitivity and 71% specificity 24 h after intubation. The AUC of our VAP machine learning model is nearly 25% higher than the CPIS model, and the sensitivity and specificity were also improved by almost 14% and 15%, respectively. Conclusions We developed and internally validated an automated model for VAP prediction using the MIMIC-III cohort. The VAP prediction model achieved high performance based on its AUC, sensitivity and specificity, and its performance was superior to that of the CPIS model. External validation and prospective interventional or outcome studies using this prediction model are envisioned as future work.

Abstract Background Calcific aortic valve stenosis (CAVS) represents a serious health threat to elderly patients. Post-stenotic aortic dilation, a common feature in CAVS patients, might progress into aneurysm and even dissection, potential consequences of CAVS, and predicts a poor prognosis. This study sought to investigate the association of lymphocyte-to-monocyte ratio (LMR), an inflammatory biomarker, with severe post-stenotic aortic dilation in a case–control study in Chinese population. Materials and methods 208 consecutive patients with CAVS were recruited retrospectively in a case–control study in Chinese population, from July 1, 2015 to June 31, 2018. LMR was statistically analyzed using the ROC curve and binary logistic regression analyses for its prognostic value in severe post-stenotic aortic dilation. Results LMR was significantly reduced in patients with severe post-stenotic aortic dilation (2.72 vs. 3.53, p = 0.002

Abstract Background The anticoagulant treatment and clinical efficacy of heparin in sepsis remains controversial. We conducted a meta-analysis to estimate the clinical efficacy of unfractionated heparin (UFH) in adult septic patients. Method A systematic review of Medline, Cochrane Library, PubMed, Embase, WEIPU database, CNKI database, WANFANG database was performed from inception to January 2021. We included Randomized controlled trials (RCTs) and the main outcome was 28 d mortality. Data analysis was performed with Review Manager (RevMan) version 5.3 software. The meta-analysis included 2617 patients from 15 RCTs. Results Comparing to control group, UFH could reduce 28 d mortality (RR: 0.82; 95% CI: 0.72 to 0.94) especially for patient with Acute Physiology and Chronic Health Evaluation II (APACHE II) > 15, (RR: 0.83; 95% CI: 0.72 to 0.96). In UFH group, the platelet (PLT) (MD: 9.18; 95% CI: 0.68 to 17.68) was higher, the activated partial thromboplastin time (APTT) was shorter (MD: -8.01; 95% CI: − 13.84 to − 2.18) and the prothrombin time (PT) results (P > 0.05) failed to reach statistical significance. UFH decreased multiple organ dysfunction syndrome (MODS) incidence (RR: 0.61; 95% CI: 0.45 to 0.84), length of stay (LOS) in ICU (MD: -4.94; 95% CI: − 6.89 to − 2.99) and ventilation time (MD: -3.01; 95% CI: − 4.0 to − 2.02). And UFH had no adverse impact on bleeding (RR: 1.10; 95% CI: 0.54 to 2.23). Conclusion This meta-analysis suggests that UFH may reduce 28 d mortality and improve the clinical efficacy in sepsis patients without bleeding adverse effect.

Sepsis is frequently associated with hemostasis activation and thrombus formation, and systematic hemostatic changes are associated with a higher risk of mortality. The key events underlying hemostasis activation during sepsis are the strong activation of innate immune pathways and the excessive inflammatory response triggered by invading pathogens. Pyroptosis is a proinflammatory form of programmed cell death, that defends against pathogens during sepsis. However, excessive pyroptosis can lead to a dysregulation of host immune responses and organ dysfunction. Recently, pyroptosis has been demonstrated to play a prominent role in hemostasis activation in sepsis. Several studies have demonstrated that pyroptosis participates in the release and coagulation activity of tissue factors. In addition, pyroptosis activates leukocytes, endothelial cells, platelets, which cooperate with the coagulation cascade, leading to hemostasis activation in sepsis. This review article attempts to interpret the molecular and cellular mechanisms of the hemostatic imbalance induced by pyroptosis during sepsis and discusses potential therapeutic strategies.

ABSTRACT Japanese encephalitis virus (JEV) genotype V (GV) emerged in China in 2009, then South Korea, and has since spread to other regions in Asia and beyond, raising concern about its pathogenicity and the cross-protection offered by JEV vaccines against different genotypes. In this study, we replaced the structural proteins (C-prM-E) of an attenuated genotype I (GI) SD12-F120 strain with those of a virulent GV XZ0934 strain to construct a recombinant chimeric GI-GV JEV (JEV-GI/V) strain to determine the role of the structural proteins in virulence and cross-protection. The recombinant chimeric virus was highly neurovirulent and neuroinvasive in mice. This demonstrated the determinant role of the structural proteins in the virulence of the GV strain. Intracerebral or intraperitoneal inoculation of mice with JEV-GI/V-E5 harboring a combination of substitutions (N47K, L107F, E138K, H123R, and I176R) in E protein, but not mutants containing single substitution of these residues, resulted in decreased or disappeared mortality, suggesting that these residues synergistically, but not individually, played a role in determining the neurovirulence and neuroinvasiveness of the GV strain. Immunization of mice with attenuated strain JEV-GI/V-E5 provided complete protection and induced high neutralizing antibody titers against parental strain JEV-GI/V, but partial cross-protection and low cross-neutralizing antibodies titers against the heterologous GI and GIII strains in mice, suggesting the reduced cross-protection of JEV vaccines among different genotypes. Overall, these findings suggested the essential role of the structural proteins in determination of the virulence of GV strain, and highlighted the need for a novel vaccine against this newly emerged strain. IMPORTANCE The GV JEV showed an increase in epidemic areas, which exhibited higher pathogenicity in mice than the prevalent GI and GIII strains. We replaced a recombinant chimeric GI-GV JEV (JEV-GI/V) strain to determine the role of the structural proteins in virulence and cross-protection. It was found that the essential role of the structural proteins is to determinethe virulence of the GV strain. It is also suggested that there is reduced cross-protection of JEV vaccines among different genotypes, which provides basic data for subsequent JEV prevention, control, and new vaccine development.

African Swine Fever (ASF) is an acute, highly contagious and deadly infectious disease that has a huge impact on the swine industry. It is caused by the African swine fever virus (ASFV). The most acute forms of ASF in domestic pigs have mortality rates of up to 100%. The lack of a commercial vaccine and effective therapeutic drugs has brought great challenges to the prevention and control of ASF. Current, the African swine fever virus requires a huge amount of detection, so there is a need for more sensitive and accurate detection technology. The protein pB602L, as a late non-structural protein, has a high corresponding antibody titer and strong antigenicity in infected swine. In this research, the B602L gene was constructed into the pColdI prokaryotic expression vector, and prokaryotic expression of the soluble pB602L protein was induced by IPTG. Western blot analysis demonstrated that the protein had strong immunogenicity. We established an indirect ELISA method for the detection of anti-ASFV using purified recombinant pB602L protein as antigen. The detection method showed excellent specificity without cross-reactions with antibodies against PRRSV, CSFV, JEV, and GETV. The method could detect anti-ASFV in serum samples that were diluted up to 6,400 times, showing high sensitivity. The coefficients of variation of the intra-assay and inter-assay were both

BackgroundBoth catheter left atrial appendage occlusion combined with ablation (COA) and thoracoscopic surgical left atrial appendage clipping combined with ablation (TCA) have shown favorable outcomes in management of patients with atrial fibrillation (AFib). However, studies comparing the endpoints of both techniques are still lacking. Herein, a meta-analysis of safety and efficacy outcomes of COA versus TCA was performed in patients with AFib.MethodsPubmed, Embase, Cochrane, and Web of Science databases were searched for retrieving potential publications. The primary outcome was the incidence of stroke during follow-up period of at least 12 months. Secondary outcomes were acute success rate of complete left atrial appendage (LAA) closure by COA or TCA, postprocedural mortality and complications, and all-cause mortality during follow-up period of at least 12 months.Results19 studies of COA containing 1,504 patients and 6 studies of TCA with 454 patients were eligible for analysis. No significant difference in stroke and all-cause mortality was found in patients undergoing COA versus TCA after at least a 12-month follow-up (stroke: p = 0.504; all-cause mortality: p = 0.611). COA group had a higher acute success rate compared with TCA group (p = 0.001). COA placed the patients at a higher risk of hemorrhage during the postprocedural period compared with TCA (p = 0.023). A similar risk of other postprocedural complications (stroke/transient ischemic attack and pericardial effusion) and mortality was found in the COA group in comparison with TCA group (p>0.05).ConclusionThis meta-analysis showed that COA and TCA did not differ in stroke prevention and all-cause mortality in patients with AFib after a follow-up of at least 12 months. Postprocedural complications and mortality were almost comparable between the two groups. In the near future, high-quality randomized controlled trials exploring the optimal surgical strategies for AFib and endpoints of different procedures are warranted.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022325497].

Coagulopathy, characterized by a high D-dimer level, is a common pathological occurrence in coronavirus disease 2019 (COVID-19) and is associated with poor prognosis. Severe cases with COVID-19 is associated with a significantly higher risk of deep vein thrombosis and acute pulmonary embolism. Pulmonary intravascular coagulopathy is the characteristic coagulopathy in COVID-19. Unlike sepsis-induced coagulopathy and disseminated intravascular coagulation, which are manifestations of systemic coagulopathy, pulmonary intravascular coagulopathy is a manifestation of a local coagulation disorder in the lung. The progression from pulmonary intravascular coagulopathy to sepsis-induced coagulopathy or disseminated intravascular coagulation in the context of COVID-19 may indicate that the patient's coagulation dysfunction has progressed from local to systemic. Exploring the associated coagulation disease will aid in the understanding of the pathophysiological mechanisms underlying severe COVID-19.

Abstract Background Soluble CD40 ligand (sCD40L) exhibits proinflammatory and procoagulant effects. Recent data indicated that sCD40L plays a significant role in septic patients. The aim of the present study was to determine sCD40L changes in surgical patients without sepsis (SWS) and surgical sepsis patients (SS) during the first 3 days after intensive care unit (ICU) admission and to observe the association between sCD40L and mortality. Methods Time changes in sCD40L levels were assessed for 3 days after ICU admission in 49 patients with SS and compared with those in 19 SWS patients. Serum sCD40L concentration was detected by ELISA. Survival at 28 days served as the endpoint. Results SS had significantly higher sCD40L levels than SWS and control patients. We observed an association between sCD40L levels ≥1028.75 pg/mL at day 2 and 28-day mortality (odds ratio = 7.888; 95% confidence interval = 1.758 to 35.395; P = 0.007). We could not discover any significant differences in sex, presence of septic shock, site of infection, length of stay in the ICU, PaO2/FiO2 ratio, incidence of AKI, ARDS, or type of surgery between nonsurvivors and survivors. Conclusions Septic patients show persistently higher circulating sCD40L levels in the first 3 days after ICU admission, and serum sCD40L levels are associated with the mortality of patients with sepsis. Thus, serum sCD40L may be used as a reliable biomarker and therapeutic target in sepsis.

Background Acute kidney injury (AKI) is widespread in the intensive care unit (ICU) and affects patient prognosis. According to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, the absolute and relative increases of serum creatinine (Scr) are classified into the same stage. Whether the prognosis of the two types of patients is similar in the ICU remains unclear. Methods According to the absolute and relative increase of Scr, AKI stage 1 and stage 3 patients were divided into stage 1a and 1b, stage 3a and 3b groups, respectively. Their demographics, laboratory results, clinical characteristics, and outcomes were analyzed retrospectively. Results Of the 345 eligible cases, we analyzed stage 1 because stage 3a group had only one patient. Using 53 or 61.88 µmol/L as the reference Scr (Scrref), no significant differences were observed in ICU mortality (P53=0.076, P61.88=0.070) or renal replacement therapy (RRT) ratio, (P53=0.356, P61.88=0.471) between stage 1a and 1b, but stage 1b had longer ICU length of stay (LOS) than stage 1a (P53

Candida auris is an emerging pathogenic fungal species found worldwide. Since April 2016, C. auris colonization/infection cases have been found in a general hospital in Shenyang, China. The genome-based phylogenetic studies of these isolates remain undefined. In the current study, the microbiological characteristics and antifungal susceptibility of these C. auris isolates, which were collected in Shenyang during the three-year period (2016–2018), were investigated. Whole-genome sequencing was applied to investigate the genetic variation and molecular epidemiological characteristics. A total of 93 C. auris isolates, including 92 clinical isolates and 1 environmental screening isolate were identified. Among the investigated wards, the C. auris cases were the most prevalent (97.4%, 37/38) in four intensive care units (ICUs). The Shenyang isolates carrying the VF125AL mutation in the key drug-resistance gene ERG11 were mainly fluconazole resistant and formed a distinct subclade under the South African clade according to the phylogenetic and population structural analyses. In addition, the Shenyang subclade was found to be closely related to the British subclade in the aspect of genetic distance. As a conclusion, this study provides an important clue for revealing the origin of C. auris found in Shenyang and could also contribute to improve the understanding of the epidemiological characteristics of C. auris worldwide.

Magnesium-lithium (Mg-Li) alloys have become promising metal engineering materials due to the outstanding weight reduction performance. However, the vulnerability to corrosion is a major obstacle for development. A variety of surface treatment methods have been applied to protect Mg-Li alloys against corrosion deterioration, among which micro-arc oxidation (MAO) is an effective and economic method. Additionally, MAO coatings also present high hardness, excellent wear resistance, and strong bonding to the substrate. This article reviews advances in MAO coatings on Mg-Li alloys, which includes summarizations for the MAO parameters and factors affecting the properties of the coatings. The main focus is given to characteristics of the MAO coatings on Mg-Li alloys, as well as the functionalization performance in a wide application.

Abstract Background The acute kidney injury (AKI) remains a frequent complication following open thoracic aortic surgery (OTAS) and worsens the postoperative prognosis. It remains unclear that whether the predictors of AKI following OTAS are different in the patients with or without acute aortic syndrome (AAS). Methods Preoperative and intraoperative variables were compared between the patients with or without AKI, and were further analyzed for identifying the potential predictors of postoperative AKI. Subgroup analysis was conducted in the patients with or without AAS, respectively. Results AKI after OTAS occurred in 57.6% of the overall cohort, 70.1% of the patients with AAS and 46.7% of the patients without AAS. In the multivariate analysis, history of hypertension (OR 1.011, 95% CI: [1.001–1.022], p = 0.04), preoperative platelet (OR 0.995, 95% CI: [0.991–0.999], p = 0.006) and operation time (OR 1.572, 95% CI: [1.355–1.823], p

Abstract In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) was identified in Wuhan, China. The World Health Organization (WHO) declared this outbreak a significant threat to international health. COVID-19 is highly infectious and can lead to fatal comorbidities especially acute respiratory distress syndrome (ARDS). Thus, fully understanding the characteristics of COVID-19-related ARDS is conducive to early identification and precise treatment. We aimed to describe the characteristics of COVID-19-related ARDS and to elucidate the differences from ARDS caused by other factors. COVID-19 mainly affected the respiratory system with minor damage to other organs. Injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS, and endothelial cells were less damaged with therefore less exudation. The clinical manifestations were relatively mild in some COVID-19 patients, which was inconsistent with the severity of laboratory and imaging findings. The onset time of COVID-19-related ARDS was 8–12 days, which was inconsistent with ARDS Berlin criteria, which defined a 1-week onset limit. Some of these patients might have a relatively normal lung compliance. The severity was redefined into three stages according to its specificity: mild, mild-moderate, and moderate-severe. HFNO can be safe in COVID-19-related ARDS patients, even in some moderate-severe patients. The more likely cause of death is severe respiratory failure. Thus, the timing of invasive mechanical ventilation is very important. The effects of corticosteroids in COVID-19-related ARDS patients were uncertain. We hope to help improve the prognosis of severe cases and reduce the mortality.

Abstract The seasonal variations of blood lipids have recently gained increasing interest in this field of lipid metabolism. Elucidating the seasonal patterns of blood lipids is particularly helpful for the prevention and treatment of cardiovascular and cerebrovascular diseases. However, the previous results remain controversial and the underlying mechanisms are still unclear. This mini-review is focused on summarizing the literature relevant to the seasonal variability of blood lipid parameters, as well as on discussing its significance in clinical diagnoses and management decisions.

Abstract Background There is a complex interplay between inflammatory response and coagulation in sepsis. Heparin is used as a recognized anticoagulant and possesses multiple biological properties that possibly affect sepsis. This study aimed to determine the possible signaling pathways involved in the anti-inflammatory effects of unfractionated heparin (UFH) on lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs). Methods HPMECs were transfected with siRNA targeting IκB-α. Cells were treated with UFH (0.01 U/ml~ 10 U/ml) 15 min before adding LPS (10 μg/ml). We detected the markers of systemic inflammatory response. Release of interleukin (IL)-6, IL-8 were evaluated at 3 h by ELISA and at 1 h by qRT-PCR. After 1 h, nuclear factor-κB (NF-κB) as well as phosphorylated inhibitor κB-α (IκB-α), signal transducer and activator of transcription-3 (STAT3) and ERK1/2, JNK, p38 mitogen-activated protein kinase (MAPK) expressions were evaluated by Western blot. DNA binding was conducted to further prove the activation of NF-κB pathway. Results In HPMECs, UFH obviously inhibited LPS-stimulated production of IL-6 and IL-8, especially in 10 U/ml. UFH inhibited LPS-induced phosphorylation of IκB-α, ERK1/2, JNK, p38 MAPK and STAT3. UFH also suppressed LPS-stimulated nuclear translocation of NF-κB. Importantly, transfection with siRNA targeting IκB-α induced more obvious inflammatory response. UFH suppressed cytokines production and phosphorylation of different signaling pathways in IκB-α silencing cells. Conclusion These results demonstrate that UFH exerts the anti-inflammatory effects on LPS-stimulated HPMECs by different signaling pathways.

Abstract Background Prolonged and difficult weaning is associated with higher rates of complications and mortality. Therefore, it is important to identify the associated factors. Case presentation We describe our experience with a 37-year-old man diagnosed with severe viral pneumonia (influenza A). He presented with acute respiratory failure type I on admission. During intubation, his blood pressure and heart rate decreased, and epinephrine and norepinephrine were administered. Although his clinical condition improved 8 days after intensive care unit (ICU) admission, he experienced difficulty weaning. He remained conscious but had a poor spontaneous cough with sputum production and weak limb muscle strength. His cough reflex was absent during bronchoscopic sputum suction, and he used abdominal breathing during the T-tube test. Magnetic resonance imaging revealed an Arnold–Chiari malformation type I, posterior dislocation of the odontoid process, and syringomyelia, with compression and deformation of the medulla and high cervical cord. The patient was successfully weaned from the ventilator at 20 days after ICU admission. Conclusions Arnold–Chiari malformation type I and posterior dislocation of the odontoid process, which aggravate medullary compression and increase the risk of cervical nerve injury, might be a rare factor affecting prolonged weaning in critical illness.

BackgroundThis study examined the role of blood urea nitrogen-to-albumin ratio (BAR) in predicting long-term mortality in patients undergoing coronary artery bypass grafting (CABG).MethodsIn this retrospective cohort study, patients undergoing CABG were enrolled from the Medical Information Mart for Intensive Care III (MIMIC III) database. Patients were divided into the three groups according to the optimal cutoff values of BAR determined by X-tile software. The survival curve was constructed by the Kaplan–Meier method and multivariate Cox regression analysis was performed to explore the independent prognostic factors of 1- and 4-year mortality after CABG. The receiver operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were calculated to estimate the accuracy of BAR in predicting the outcomes. Subgroup analyses were also carried out.ResultsA total of 1,462 patients at 4-year follow-up were included, of which 933, 293, and 236 patients were categorized into the group 1 (≤ 6.45 mg/g), group 2 (>6.45 and ≤ 10.23 mg/g), and group 3 (>10.23 mg/g), respectively. Non-survivors showed an increased level of BAR at both 1- (p < 0.001) and 4-year (p < 0.001) follow-up compared with the survivors. The patients with a higher BAR had a higher risk of 1- and 4-year mortality following CABG (33.05 vs. 14.33 vs. 5.14%, p < 0.001 and 52.97 vs. 30.72 vs. 13.08%, p < 0.001, respectively). Cox proportional hazards regression model suggested a higher BAR as an independent risk factor of 1-year mortality (HR 3.904; 95% CI 2.559–5.956; P < 0.001) and 4-year mortality (HR 2.895; 95% CI 2.138–3.921; P < 0.001) after adjusting for confounders. Besides, the receiver operating characteristic (ROC) curves showed the better predictive ability of BAR compared to other grading scores at both 1- (0.7383, 95% CI: 0.6966–0.7800) and 4-year mortality (0.7189, 95% CI: 0.6872–0.7506). Subgroup analysis demonstrated no heterogeneous results of BAR in 4-year mortality in particular groups of patient.ConclusionThis report provided evidence of an independent association between 1- and 4-year mortality after CABG and BAR. A higher BAR was associated with a higher risk of long-term mortality and could serve as a prognostic predictor in patients following CABG.

Body-centered cubic (BCC) Mg–Li alloy can be effectively strengthened by with the addition of Al and Zn. However, adding excessive amounts result in reduced mechanical properties and damping capacity of the alloy during subsequent heat treatment and deformation. The effects of solution-hot rolling-aging on the mechanical properties and damping capacity of LAZ1333 alloy and LAZ1366 alloy were studied. The solid solution strengthening greatly increases the hardness of the alloy, but the ductility is extremely poor. The AlLi softening phase precipitated during the subsequent hot rolling and aging process greatly improves the ductility of the alloy, but the excess precipitation of in the AlLi softening phase and the solid solution of excess Zn element are not conducive to the substantial improvement of the strength and ductility of the alloy. Excessive addition of alloying elements is detrimental to the damping capacity of the alloy, but the damping capacity of the alloy can be significantly improved by depleting the number of solute atoms through subsequent ageing treatments. The UTS and FE of as-cast LAZ 1333 alloy are 111 MPa and 16.9%, respectively. The as-aged LAZ1333 alloy has the best mechanical properties and damping capacity, and the UTS and FE are increased by 65.8% and 89.3%, respectively, compared to the as-cast alloy, and the damping capacity increased from 0.011 to 0.015.

Streptococcus suis is a significant pathogen in pigs and a newly emerging zoonotic agent in humans. The presence of multiple serotypes and strains with diversified sequence types in pig herds highlights the need for the identification of broadly cross-reactive universal vaccine antigen targets, capable of providing cross-protection against S. suis infection. Subunit vaccines based on the conserved proteins shared between different S. suis serotypes are potential candidates for such a universally protective vaccine. In the present study, phosphate ABC transporter ATP-binding protein PstB (PstB), an immunogenic protein of the S. suis bacterium, was expressed and purified, and then subjected to cross-protection evaluation in mice. The PstB protein showed nearly 100% amino acid similarity across a panel of 31 S. suis isolates representing different serotypes, which were collected from different countries. A recombinant PstB (rPstB) protein (S. suis serotype 2) was recognized by rabbit sera specific to this serotype, and induced high levels of IFN-γ and IL-4 in mice immunized with the recombinant protein. These cytokines are considered important for protection against S. suis infection. Immunization of mice with rPstB resulted in an 87.5% protection against challenge with S. suis serotype 2 and 9 strains, suggesting a high level of cross-protection for S. suis serotypes 2 and 9. A lower protection rate (62.5%) was observed in mice challenged with the S. suis serotype 7 strain. These data demonstrate that PstB is a promising target antigen for development as a component of a universal subunit vaccine against multiple S. suis serotypes.

In this study, we deformed the single β phase Mg–Li alloy, Mg–16Li–4Zn–1Er (LZE1641), with conventional rolling (R) and multi-directional rolling (MDR), both at cryogenic temperature. Results showed that the nano-precipitation phase MgZn2 appeared in the alloy after MDR, but this phenomenon was not present in the alloy after R. The finite element simulation result showed that the different deformation modes changed the stress distribution inside the alloy, which affected the microstructures and the motion law of the solute atoms. The high-density and dispersively distributed MgZn2 particles with a size of about 35 nm were able to significantly inhibit the grain boundary migration. They further hindered the dislocation movement and consolidated the dislocation strengthening and fine-grain strengthening effects. Compared with the compressive strength after R (273 MPa), the alloy compressive strength was improved by 21% after MDR (331 MPa). After 100 °C compression, the MgZn2 remained stable.

Background: Lung-protective ventilation (LPV) strategies have been beneficial in patients with acute respiratory distress syndrome (ARDS). As a vital part of LPV, positive end-expiratory pressure (PEEP) can enhance oxygenation. However, randomized clinical trials of different PEEP strategies seem to show no advantages in clinical outcomes in patients with ARDS. A potential reason is that diverse etiologies and phenotypes in patients with ARDS may account for different PEEP responses, resulting in variations in mortality. We consider hospital mortality to be associated with a more specific classification of ARDS, such as sepsis induced or not, and pulmonary or extrapulmonary one. Our study aimed to compare clinical outcomes in various patients with ARDS by etiologies using the China Critical Care Sepsis Trial (CCCST) database. This was a retrospective analysis of a prospective cohort of 2,138 patients with ARDS in the CCCST database. According to ARDS induced by sepsis or not and medical history, patients were stratified into different four groups. Differences among groups were assessed in hospital mortality, ventilation-free days, and other clinical features.Results: A total of 2,138 patients with ARDS were identified in the database, including 647 patients with sepsis-induced pulmonary ARDS (30.3%), 396 patients with sepsis-induced extrapulmonary ARDS (18.5%), 536 patients with non-sepsis pulmonary ARDS (25.1%), and 559 patients with non-sepsis extrapulmonary ARDS (26.1%). The pulmonary ARDS group had higher mortality compared with the extrapulmonary group (45.9 vs. 23.0%, p < 0.01), longer intensive care unit (ICU) and hospital stays (9 vs. 6 days, p < 0.01, 20 vs. 18 days, p = 0.01, respectively), and fewer ventilation-free days (5 vs. 9 days) in the presence of sepsis. However, the mortality in ARDS without sepsis was inverted compared with extrapulmonary ARDS (pulmonary 23.5% vs. extrapulmonary 29.2%, p = 0.04). After adjusting for the Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores and other clinical features, the sepsis-induced pulmonary condition was still a risk factor for death in patients with ARDS (hazard ratio 0.66, 95% CI, 0.54–0.82, p < 0.01) compared with sepsis-induced extrapulmonary ARDS and other subphenotypes.Conclusions: In the presence of sepsis, hospital mortality in pulmonary ARDS is higher compared with extrapulmonary ARDS; however, mortality is inverted in ARDS without sepsis. Sepsis-induced pulmonary ARDS should attract more attention from ICU physicians and be cautiously treated.Trial registration: ChiCTR-ECH-13003934. Registered August 3, 2013, http://www.chictr.org.cn.

The frequent detection of (2,3-dibromopropyl) phosphate (TDBPP) in environment has led to a consistent risk to organisms. However, little is known about the toxicity of TDBPP exclusive for its carcinogen. Mitochondrion that tightly relates to adverse outcomes once deteriorated is referred as a target of environmental pollutants. Here, we investigated the role of mitochondrial abnormality in development of cellular pathobiology especially lipid deposition when response to TDBPP in mitochondria-rich hepatocyte (AML12) at the same order of magnitude as the environmental concentrations (10−6 mol/L or below) via multiplexed quantitative high content analytic system. The present study claimed TDBPP shifted mitochondria from fusion morphology to fission phenotype charactering by less mitochondrial networks, larger mitochondrial areas and shorter branch length at 10−7 mol/L or above. This dynamic imbalance was triggered by high levels of fis and drp1 genes when treated with TDBPP. The deformation caused by TDBPP reciprocally influenced biogenesis through PGC1α and electron transport chains via ectopic expression of genes encoding for mitochondria complex I and III subunits. Accordingly, we observed high mitoROS level and low mitochondria membrane potential. Consequently, cells contained those abnormal mitochondria were predisposed to accumulating lipids after exposure to TDBPP. Here we showed that TDBPP deteriorated mitochondrial morphology and function, which may induce lipid generation. As for a banned while still emerged contaminant, our study also claimed further exploration on the non-carcinogenic toxicity of TDBPP.

Background: The post-operative acute kidney injury (AKI) represents a common complication in the Acute Debakey Type I Aortic Dissection (ADTIAD) and predicts a poorer prognosis. The clinical evidence is scarce supporting the predictive value of the pre-operative lymphocyte-to-monocyte ratio (LMR) in post-operative AKI in ADTIAD.Methods: In this retrospective cohort study, 190 consecutive patients with ADTIAD enrolled for surgical treatment between January 1, 2013, and December 31, 2018. The diagnosis of AKI followed the Kidney Disease: Improving Global Outcomes guidelines (KDIGO). Pre-operative LMR and other possible risk factors were analyzed for their prognostic value in the post-operative AKI in ADTIAD.Results: The subjects were assigned to the low-LMR and high-LMR groups according to the median value of pre-operative LMR. For post-operative AKI, the incidence and the severity in the low-LMR group were statistically different from that of the high-LMR group. Besides, the lower LMR was statistically associated with the more extended ICU stay and intubation time and higher incidences of ischemic stroke and in-hospital mortality. Additionally, in the multivariable analysis, the pre-operative LMR was an independent predictor for post-operative AKI in ADTIAD. A predictive model for post-operative AKI in ADTIAD was established incorporating LMR.Conclusions: LMR is an independent prognostic indicator incorporated into the predictive model with other risk factors to predict the post-operative AKI in ADTIAD.

Background. Alterations of microcirculation are associated with organ hypoperfusion and high mortality in septic shock. This study is aimed at investigating the effects of unfractionated heparin (UFH) on intestinal microcirculatory perfusion and systemic circulation in a septic shock model. Methods. Twenty-four beagle dogs were randomly allocated into four groups: (a) sham group: healthy controls, (b) shock group: septic shock induced by Escherichia coli, (c) basic therapy group: septic shock animals treated with antibiotics and 10 ml/kg/h saline, and (d) heparin group: septic shock animals treated with basic therapy plus UFH. Hemodynamic variables were measured within 24 h after E. coli administration. The intestinal microcirculation was simultaneously investigated with a sidestream dark-field imaging technique. Additionally, the function of vital organs was evaluated at 12 h postadministration (T12). Results. E. coli induced a progressive septic shock in which the mean arterial pressure (MAP) decreased and lactate levels sharply increased, accompanied by deteriorated microvessel perfusion. While basic therapy partially improved the microvascular flow index and the perfused microvessel density in the jejunal villi, UFH significantly restored major microcirculation variables at T12. Physiological variables, including MAP, urine output, and lactate levels, were improved by UFH, whereas some hemodynamic indices were not affected by UFH. With respect to organ function, UFH increased the platelet count and decreased the creatinine level. Conclusions. UFH improves microcirculatory perfusion of the small intestine independently of the changes in systemic hemodynamic variables in a canine model of septic shock, thereby improving coagulation and renal function.

Background: Sepsis is a main cause of morbidity and mortality in critically ill patients. The epidemiology of sepsis in high-income countries is well-known, but information on sepsis in middle- or low-income countries is still deficient, especially in China. The purpose of this study was to explore the prevalence, characteristics, risk factors, treatment, and outcomes of sepsis in critically ill patients in tertiary hospitals in China.Methods: A multicenter prospective observational cohort study was performed with consecutively collected data from adults who stayed in any intensive care unit (ICU) for at least 24 h; data were collected from 1 January 2014 to 31 August 2015, and patients were followed until death or discharge from the hospital.Results: A total of 4,910 patients were enrolled in the study. Of these, 2,086 (42.5%) presented with sepsis or septic shock on admission to the ICU or within the first 48 h after admission to the ICU. ICU mortality was higher in patients with sepsis (13.1%) and septic shock (39.0%) and varied according to geographical region. Acinetobacter, Pseudomonas, and Staphylococcus infections were associated with increased ICU mortality. In addition, age, Acute Physiology, and Chronic Health Evaluation II (APACHE II) scores, pre-existing cardiovascular diseases, malignant tumors, renal replacement therapy (RRT), and septic shock were independent risk factors for mortality in patients with sepsis. The prompt administration of antibiotics (OR 0.65, 95% CI 0.46–0.92) and 30 mL/kg of initial fluid resuscitation during the first 3 h (OR 0.43, 95% CI 0.30–0.63) improved the outcome in patients with septic shock.Conclusions: Sepsis was common and was associated with a high mortality rate in critically ill patients in tertiary hospitals in China. The prompt administration of antibiotics and 30 mL/kg fluid resuscitation decreased the risk of mortality.

Nonstructural protein 2A (NS2A) of the Japanese encephalitis virus (JEV) contributes to viral replication and pathogenesis; however, a lack of NS2A-specific antibodies restricts studies on the underlying mechanisms. In this study, we constructed a recombinant JEV with a hemagglutinin (HA)-tagged NS2A (JEV-HA/NS2A/∆NS1’) to overcome this challenge. An HA-tag was fused to the N-terminus of NS2A (HA-NS2A) at the intergenic junction between NS1 and NS2A. A peptide linker, “FNG”, was added to the N-terminus of HA-tag to ensure correct cleavage between the C-terminus of NS1 and the N-terminus of HA-NS2A. To avoid the side effects of an unwanted NS1’ tagged with HA (HA-NS1’), an alanine-to-proline (A30P) substitution was introduced at residue 30 of NS2A to abolish HA-NS1’ production. The HA-tag insertion and A30P substitution were stably present in JEV-HA/NS2A/∆NS1’ after six passages and did not exhibit any significant effects on viral replication and plaque morphology. Taking advantage of HA-NS2A, we examined the activities of NS2A during JEV infection in vitro using anti-HA antibodies. NS2A was observed to be localized to the endoplasmic reticulum and interact with viral NS2B and NS3 during virus infection. These data suggest that JEV-HA/NS2A/∆NS1’ can serve as a model for the analysis of the biological characteristics and functions of NS2A in vitro during JEV infection.

Japanese encephalitis virus (JEV) genotype I (GI) replicates more efficiently than genotype III (GIII) in birds, and this difference is considered to be one of the reasons for the JEV genotype shift. In this study, we utilized duck embryo fibroblasts and domestic ducklings as in vitro and in vivo models of a JEV amplifying avian host to identify the viral determinants of the differing replication efficiency between the GI and GIII strains in birds. GI strains induced significantly lower levels of interferon (IFN)-α and β production than GIII strains, an effect orrelated with the enhanced replication efficiency of GI strains over GIII strains. By using a series of chimeric viruses with exchange of viral structural and non-structural (NS) proteins, we identified NS5 as the viral determinant of the differences in IFN-α and β induction and replication efficiency between the GI and III strains. NS5 inhibited IFN-α and β production induced by poly(I:C) stimulation and harbored 11 amino acid variations, of which the NS5-V372A and NS5-H386Y variations were identified to co-contribute to the differences in IFN-α and β induction and replication efficiency between the strains. The NS5-V372A and NS5-H386Y variations resulted in alterations in the number of hydrogen bonds formed with neighboring residues, which were associated with the different ability of the GI and GIII strains to inhibit IFN-α and β production. Our findings indicated that the NS5-V372A and NS5-H386Y variations enabled GI strains to inhibit IFN-α and β production more efficiently than GIII strains for antagonism of the IFN-I mediated antiviral response, thereby leading to the replication and host adaption advantages of GI strains over GIII strains in birds. These findings provide new insight into the molecular basis of the JEV genotype shift.

Objective This study aimed to evaluate the duration of intensive care unit (ICU) stay prior to onset of invasive candidiasis (IC)/candidaemia.Design Systematic review and meta-analysis.Data sources PubMed, Cochrane, Embase and Web of Science databases were searched through June 2019 to identify relevant studies.Eligibility criteria Adult patients who had been admitted to the ICU and developed an IC infection.Data extraction and synthesis The following data were extracted from each article: length of hospital stay, length of ICU stay, duration of ICU admission prior to candidaemia onset, percentage of patients who received antibiotics and duration of their antibiotic therapy prior to candidaemia onset, and overall mortality. In addition to the traditional meta-analyses, meta-regression was performed to explore possible mediators which might have contributed to the heterogeneity.Results The mean age of patients ranged from 28 to 76 years across selected studies. The pooled mean duration of ICU admission before onset of candidaemia was 12.9 days (95% CI 11.7 to 14.2). The pooled mean duration of hospital stay was 36.3±5.3 days (95% CI 25.8 to 46.7), and the pooled mean mortality rate was 49.3%±2.2% (95% CI 45.0% to 53.5%). There was no significant difference in duration of hospital stay (p=0.528) or overall mortality (p=0.111), but a significant difference was observed in the mean length of ICU stay (2.8 days, p

Background. gp91phox, the catalytic core of NADPH oxidase (NOX) and biomarker of NOX activation, has been recently recognized as a parameter of systemic oxidative stress in several studies. Subclinical hypothyroidism (SH) is characteristic of elevated level of serum thyroid stimulating hormone (TSH) and is frequently accompanied with cholesterolemia. In this study, the levels of serum soluble gp91phox were measured to assess the oxidative stress in patients with SH. And the relationship among gp91phox, low-density lipoprotein-C (LDL-C), and TSH was also investigated. Methods. A total of 51 subjects were enrolled and categorized into four groups: the healthy controls subjects (n = 13), controls with high level of LDL-C alone (n = 12), SH with normal level of LDL-C (n = 11), and SH with high level of LDL-C (n = 15). The related clinical and laboratory data were collected for statistical analysis. All the patients were newly diagnosed and did not take any medication. The information of lipid profile and thyroid function was extracted, and the concentrations of gp91phox were obtained with ELISA. Results. The levels of serum soluble gp91phox evidently increased in the patients with SH with a high level of LDL-C (81.52 ± 37.00 ug/mL) as compared to the healthy controls (54.98 ± 1.83ug/mL, p

Abstract Background Endothelial barrier dysfunction is central to the pathogenesis of sepsis-associated acute lung injury (ALI). Microtubule (MT) dynamics in vascular endothelium are crucial for the regulation of endothelial barrier function. Unfractionated heparin (UFH) possesses various biological activities, such as anti-inflammatory activity and endothelial barrier protection during sepsis. Methods Here, we investigated the effects and underlying mechanisms of UFH on lipopolysaccharide (LPS)-induced endothelial barrier dysfunction. C57BL/6 J mice were randomized into vehicle, UFH, LPS and LPS + UFH groups. Intraperitoneal injection of 30 mg/kg LPS was used to induce sepsis. Mice in the LPS + UFH group received intravenous UFH 0.5 h prior to LPS injection. Human pulmonary microvascular endothelial cells (HPMECs) were cultured for analyzing the effects of UFH on LPS-induced and nocodazole-induced hyperpermeability, F-actin remodeling, and LPS-induced p38 MAPK activation. Results UFH pretreatment significantly attenuated LPS-induced pulmonary histopathological changes, and increased the lung W/D ratio and Evans blue accumulation in vivo. Both in vivo and in vitro studies showed that UFH pretreatment blocked the LPS-induced increase in guanine nucleotide exchange factor (GEF-H1) expression and myosin phosphatase target subunit 1 (MYPT1) phosphorylation, and microtubule (MT) disassembly in LPS-induced ALI mouse model and human pulmonary microvascular endothelial cells (HPMECs). These results suggested that UFH ameliorated LPS-induced endothelial barrier dysfunction by inhibiting MT disassembly and GEF-H1 expression. In addition, UFH attenuated LPS-induced hyperpermeability of HPMECs and F-actin remodeling. In vitro, UFH pretreatment inhibited LPS-induced increase in monomeric tubulin expression and decrease in tubulin polymerization and acetylation. Meanwhile, UFH ameliorates nocodazole-induced MTs disassembly and endothelial barrier dysfunction.Additionally, UFH decreased p38 phosphorylation and activation, which was similar to the effect of the p38 MAPK inhibitor, SB203580. Conclusions UFH exert its protective effects on pulmonary microvascular endothelial barrier dysfunction via microtubule stabilization and is associated with the p38 MAPK pathway.

Background/Aims: The high mobility group box 1 (HMGB1) has been regarded as an important inflammatory mediator. Previous studies showed the involvement of HMGB1 protein in the dysfunction of endothelial barrier function during acute lung injury. However, the molecular mechanism remains unclear. Methods: In this study, we used recombinant human HMGB1 (rhHMGB1) and HMGB1 plasmid to treat human pulmonary microvascular endothelial cell (HPMECs). We examined endothelial permeability by measuring TEER value and HRP flux. Western blot and real-time PCR were used to examined change of endothelial-to-mesenchymal transition (EndoMT) markers and related pathways. Immunofluorescence was used to examine localization and expression of ZO-1 and VE-cadherin. SB203580.was used to block p38 pathway. Unfractionated heparin (UFH) and RAGE siRNA were also used to antagonize the effect of HMGB1. Results: We showed that HMGB1 induced EndoMT with downregulation of ZO-1 and VE-cadherin at both mRNA and protein levels in HPMECs. We also demonstrated that HMGB1 upregulated endothelial permeability by measuring TEER value and HRP flux. Moreover, HMGB1 activated p38/GSK3β/Snail signaling pathway and treatment with p38 inhibitor SB203580 abolished its biological effects. In addition, we found that UFH was able to reverse the effect of HMGB1 on EndoMT and endothelial permeability through inhibition of p38 signaling in a dose-dependent manner. We discovered that RAGE, a membrane receptor of HMGB1, transduced p38/Snail pathway to EndoMT. RAGE siRNA inhibited the effect of HMGB1 induced EndoMT in HPMECs. Conclusion: The present study demonstrated that HMGB1 induced EndoMT through RAGE receptor and p38/GSK3β/Snail pathway. While UFH antagonized HMGB1 and maintained the integrity of the endothelial barrier through p38 inhibition.

Abstract Background Aortic dissection (AD) represents a clinically uncommon aortic pathology which predicts a dismal prognosis if not promptly treated. In acute Debakey type I AD (ADIAD), aortic lesion extends from aortic root to even distal abdominal aorta among which aortic arch and its three main branches still remain a great surgical challenge for repair and reconstruction. Several decades have witnessed the painstaking efforts of cardiovascular surgeons across the globe for optimizing the surgical procedures, from total or hemi-arch replacement, “elephant trunk” technique to branched stent graft. However, operative mortality and morbidity still remain to be reduced and surgical strategy is to be advanced and simplified, particularly the repair and reconstruction of aortic arch and supra-aortic vessels. Methods In this paper, we reviewed the relevant literature concerning recent advances in surgical intervention of aortic arch and summarized our opinions in the application of branched stent graft in ADIAD. Results The operative strategy for acute Debakey type I aortic dissection still remain to be advanced and simplified, especially the repair and reconstruction of aortic arch and supra-aortic vessels. For selection of branched stent grafts, the anatomic features and pathological changes of diseased arch are the crucial factors for clinical decision making. Conclusions Branched stent graft is potentially an effective alternative for the treatment of type I AD with diseased aortic arch and supra-aortic vessels. The selection of branched stent grafts still remains to be further discussed in large-scale studies in the future.

Abstract Background Aorto-left ventricular tunnel (ALVT) is a rare congenital extracardiac channel that connects the ascending aorta to the left ventricle. To our knowledge, no case has been thus far reported as ALVT with both anomalous origin of right coronary artery (AORCA) and bicuspid aortic valve (BAV). Case presentation We reported a case of a 5-year-old female diagnosed as ALVT with accompanying AORCA and BAV which had been previously misdiagnosed as aortic regurgitation (AR) triggered by BAV. Additionally, a special modality of ALVT was confirmed in this case during the surgery in which the tunnel was formed by the separation between the roots of two aortic leaflets during the diastolic period. Conclusions ALVT with both AORCA and BAV is clinically uncommon and the aberrant tunnel in ALVT can be formed by the gap between the roots of two aortic leaflets. Besides, ALVT with BAV might easily lead to an inaccurate diagnose as aortic regurgitation caused by BAV. Cardiac surgeons should be alerted for differential diagnosis of ALVT with BAV and isolated bicuspid aortic valve (BAV) causing aortic regurgitation (AR).

The bias voltage-accelerated plasma was developed to investigate the in-situ wetting between liquid tin (Sn) and capillary porous system (CPS). Low wetting temperature was achieved in comparison to traditional static method. During the plasma irradiation, the correlation among temperature step, optical emission spectrum of Sn atom and wetting phenomenon was disclosed and discussed, which could provide a hint for the wetting criterion of liquid metal-CPS. The results also showed that the wetting of Sn-CPS could maintain the liquid Sn from the MHD effect, while the liquid Sn droplet would be propelled to detach from CPS for the unwetted Sn-CPS. Keywords: Liquid tin, CPS, Wetting, Temperature step, Plasma, Optical emission spectrum

Understanding the proteolytic processing of polyprotein mediated by NS2B-NS3 protease contributes to the exploration of the mechanisms underlying infection of Japanese encephalitis virus (JEV), a zoonotic flavivirus. In this study, eukaryotic and prokaryotic cell models were employed to identify the cleavage sites mediated by viral NS2B-NS3 protease in JEV polyprotein. Artificial green fluorescent protein (GFP) substrates that contained the predicted cleavage site sequences of JEV polyprotein were expressed in swine testicle (ST) cells in the presence and absence of JEV infection, or co-expressed in E. coli with the recombinant NS2B-NS3 protease that was generated by fusing the N-terminal protease domain of NS3 to the central hydrophilic domain of NS2B. The cleavage of GFP substrates was examined by western blot. Among twelve artificial GFP substrates containing the cleavage site sequences predictively processed by host cell and/or NS2B-NS3 proteases, all sites were found to be cleaved by host cell proteases with different efficiencies. The sites at internal C, NS2A/NS2B, NS2B/NS3 and NS3/NS4A junctions, but not the sites at internal NS3, internal NS4A and NS4B/NS5 junctions were identified to be cleaved by JEV NS2B-NS3 protease. These data provide insight into the proteolytic processing of polyprotein, which is useful for understanding JEV replication and pathogenesis.

In this study, In-situ precipitation reaction was used to prepare paraffin@SnO _2 /CNTs composite phase change materials. The paraffin@SnO _2 /CNTs composites material were prepared by using paraffin as a phase change core material, and tin dioxide and carbon nanotubes as composite shell materials. The microstructure, chemical composition and crystal phase structure of the composites were analyzed by Scanning electron microscope (SEM), Fourier infrared spectrum (FT-IR) and X-ray diffraction (XRD). The thermal performance and thermal stability of phase change materials were determined by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The microcapsule has a core–shell structure with a diameter of 2–5 μ m. The encapsulation efficiency of the paraffin@SnO _2 /CNTs composite was calculated to be 42.94%. The slurry is formed by dispersing microcapsules in water, which not only greatly improves the specific heat capacity, thermal conductivity, visible light absorption, but also makes the effective receiving efficiency reach 91.79% at 40 °C, indicating that it is a promising heat transfer working slurry in the field of Direct Absorption Solar Collectors (DASC) system.

BACKGROUND: The complications of atherosclerosis such as coronary and cerebrovascular disease, are the most prevalent causes of mortality and morbidity worldwide. A single nucleotide polymorphism (SNP) rs1883832 (-1C/T) in CD40 gene has been recently suggested to contribute to the susceptibility to atherosclerosis in Chinese population; however, previous genetic association studies yielded inconsistent results. METHODS: A meta-analysis of eligible studies reporting the association between rs1883832 and atherosclerosis in Chinese population was carried out. RESULTS: Pooling 7 eligible case-control studies involving 2129 patients and 1895 controls demonstrated a significant association between rs1883832 and atherosclerosis under dominant model [odds ratio (OR) = 1.631, 95% confidence interval [CI] [1.176, 2.260] in Chinese population with evident heterogeneity. Meta-regression analysis indicated that the heterogeneity could be completely explained by disease category. In subgroup analysis, rs1883832 conferred ORs of 2.866 (C/C versus T/T, 95%CI [2.203, 3.729]) and 1.680 (C/T versus T/T, 95%CI [1.352, 2.086]) for coronary artery disease (CAD) under co-dominant model without heterogeneity. Similar results were obtained for acute coronary syndrome (ACS) (C/C versus T/T, 3.674, 95%CI [2.638, 5.116]; C/T versus T/T, 1.981, 95%CI [1.483, 2.646]). The other genetic models including dominant, recessive and additive models, yielded consistent results without heterogeneity for CAD and ACS, respectively. However, a protective role was found for C allele in ischemic stroke (IS) under recessive model (0.582, 95%CI [0.393, 0.864]) and additive model (0.785, 95%CI [0.679, 0.909]) with reduced heterogeneity. CONCLUSIONS: This meta-analysis provided evidence of association of rs1883832 C allele with an overall increased risk of atherosclerosis but distinct effect of C allele on CAD (including ACS) and IS in Chinese population, respectively.