Search

Sepsis is a condition that results from a harmful or damaging host response to infection with organ dysfunction. Every year about 20 million people are dead owing to sepsis and its mortality rates is as high as 20%. However, no studies have been carried out to investigate sepsis from the system biology point of view, since previous studies mainly focused on individual genes in sepsis, ignoring the interactions and associations among the genes and transcripts. Here, we explored the expression alteration of both mRNAs and long non-coding RNAs (lncRNAs) in sepsis on a genome-wide scale, on the basis of six microarray datasets. Co-expression networks were conducted to identify mRNA and lncRNA modules, respectively. Comparing with the normal modules, we observed that the mRNA/lncRNA members in sepsis module tend to express in a homogeneous way, a majority of them are expressed in the same direction. Furthermore, consistent modules among diverse datasets were determined with 20 common mRNA members and two lncRNAs, CHRM3-AS2 and PRKCQ-AS1, which are expected to be candidate regulators of sepsis. Our results reveal that the up-regulated common mRNAs are mainly involved in the processes of neutrophil mediated immunity, while the down-regulated mRNAs and lncRNAs are significantly overrepresented in T-cell mediated immunity functions. This study concentrated on co-expression pattern of mRNAs and lncRNAs in sepsis to provide a novel perspective and insight into sepsis transcriptome, which may facilitate the exploration of candidate therapeutic targets and molecular biomarkers for sepsis.

Min Zhang,1,2 Jia Li,3 Yuemei Lu,4 Weiyuan Wu,4 Jinsong Wu,4 Yanji Xu,1,5 Yuxin Zhong,1,2 Shiyi Liu,1,2 Chuchu Lin,6 Shuye Xu,3 Dandan Chen,1,2 Xuefeng Gao,7 Yutian Luo,8 Huaisheng Chen,8 Xueyan Liu,8 Wei Huang1,2 1Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, Guangdong, People’s Republic of China; 2Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 3Department of Nosocomial Infection Control, Bengbu Third People’s Hospital, Bengbu, People’s Republic of China; 4Department of Clinical Microbiology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 5Nanshan District Center of Chronic Disease Control, Shenzhen, People’s Republic of China; 6Department of Nosocomial Infection Control, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 7Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen, People’s Republic of China; 8Department of Intensive Care Unit, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Wei HuangBacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University The First Affiliated Hospital, Southern University of Science and Technology), No. 1017 Dongmen North Road, Shenzhen People’s Hospital, Shenzhen, 518020, Guangdong, People’s Republic of ChinaTel +86 7522942513Fax +86 7522942514Email whuang_sz@163.comBackground: ST11 is the most prevalent sequence type of clinical Klebsiella pneumoniae in China.Methods: We investigated the characteristics of the ST11 subclones using core genome multi-locus sequence typing (cgMLST). Ninety-three carbapenemase-producing K. pneumoniae isolates were collected at Shenzhen People’s Hospital. Then, whole-genome sequencing and cgMLST were used to discriminate apparent subclones within the ST11 group.Results: We analyzed the prevalence and genetic relationships of these subclones. ST11 and K. pneumoniae carbapenemase (KPC-2) were the predominant genotype and carbapenemase, respectively, in the clinical carbapenemase-producing K. pneumoniae strains. cgMLST scheme genotyping divided the ST11 group into two clades across seven complex types (CTs). CT1313 was the most prevalent subclone. The deletion of galF and a high frequency of SNPs in genes associated with the stress- and SOS-responses were found in CT1291 and CT2405 over time, respectively.Conclusion: Our results indicated that the subclones of the ST11 group had different patterns of prevalence. Highly discriminatory genotyping techniques, such as cgMLST scheme, should be used in further molecular epidemiology investigations.Keywords: Klebsiella pneumoniae, whole genome sequencing, cgMLST, ST11, carbapenem-resistance

The threat of antimicrobial resistance calls for more efforts in basic science, drug discovery, and clinical development, particularly gram-negative carbapenem-resistant pathogens. We sought to identify novel antibacterial agents against Acinetobacter baumannii ATCC19606 using whole cell-based screening. A small molecule named 6D1 with the chemical structure of 6-fluorobenzo[d]isothiazol-3(2H)-one was identified and exhibited activity against A. baumannii ATCC19606 strain (minimal inhibitory concentration, MIC = 1 mg l−1). The mutation in the plasmid-derived ohrB gene that encodes a peroxidase was identified in spontaneously resistant mutants. Treatment of the bacteria with 6D1 resulted in increased sensitivity to peroxide, such as tert-butyl hydroperoxide. The binding of 6D1 and OhrB was confirmed by surface plasmon resonance. Interestingly, the MIC of kanamycin and gentamicin against spontaneously resistant mutants decreased. Finally, we identified the effect of 6D1 on enhancing the antibacterial activity of kanamycin and gentamicin, including against New Delhi metallo-β-lactamase (NDM-1)-producing carbapenem-resistant Klebsiella pneumoniae, but not in strains carrying aminoglycosides resistance genes. In this study, we identified a small molecule that suppresses the growth of A. baumannii, interacts with hydroperoxide reductase from A. baumannii ATCC19606 plasmid pMAC, and enhances the antibacterial activity of kanamycin and gentamicin. We propose that peroxidase may be potentially used as a target for aminoglycosides adjuvant development.

Sepsis is a global medical issue owing to its unacceptably high mortality rate. Therefore, an effective approach to predicting patient outcomes is critically needed. We aimed to search for a novel 28-day sepsis mortality prediction model based on serial interleukin-6 (IL-6), lactate (LAC), and procalcitonin (PCT) measurements. We enrolled 367 septic patients based on Sepsis-3 (Third International Consensus Definitions for Sepsis and Septic Shock). Serum IL-6, LAC, and PCT levels were measured serially. Results collected within 24 and 48–72 h of admission were marked as D1 and D3 (e.g., IL-6D1/D3), respectively; the IL-6, LAC, and PCT clearance (IL-6c, LACc, PCTc) at D3 were calculated. Data were split into training and validation cohorts (7:3). Logistic regression analyses were used to select variables to develop models and choose the best one according to the Akaike information criterion (AIC). Receiver operating characteristic curves (ROC), calibration plots, and decision curve analysis (DCA) were used to test model performance. A nomogram was used to validate the model. There were 314 (85.56%) survivors and 53 (14.44%) non-survivors. Logistic regression analyses showed that IL-6D1, IL-6D3, PCTD1, PCTD3, and LACcD3 could be used to develop the best prediction model. The areas under the curves (AUC) of the training (0.849, 95% CI: 0.787–0.911) and validation cohorts (0.828, 95% CI: 0.727–0.929), calibration plot, and the DCA showed that the model performed well. Thus, the predictive value of the risk nomogram was verified. Combining IL-6D1, IL-6D3, PCTD1, PCTD3, and LACcD3 may create an accurate prediction model for 28-day sepsis mortality. Multiple-center research with a larger quantity of data is necessary to determine its clinical utility.

Objective We aimed to establish a tool for rapid identification of KL49 Acinetobacter baumannii. Methods Based on the capsular polysaccharide (CPS) synthesis genes database, we investigated the distribution of K locus type 49 (KL49) genes in other KL types and established a rapid identification method for KL49. We collected 61 clinical carbapenem-resistant A. baumannii (CRAB) strains, identified KL49 by gtr100 detection, and used whole genome sequencing (WGS) for verification. A mouse pneumonia model was used to confirm the hypervirulence phenotype. We tested the presence of gtr100 gene in 165 CRAB strains from three provinces in China and evaluated the correlation of gtr100 carrying CRAB infection with mortality. Results The gtr100 gene is the CPS synthesis gene found only in KL49. We screened out nine WGS-validated KL49 strains from 61 CRAB clinical strains using polymerase chain reaction (PCR) to detect the gtr100 gene. The survival rates of KL49 strains were significantly lower than nonKL49 strains in a mouse pneumonia model. The survival rates of LAC-4 gtr100 knockout strain decreased significantly. Analysis of phylogenetics showed the worldwide spread of KL49 A. baumannii. Infection of gtr100 carrying CRAB is an independent risk for mortality (OR, 10.76; 95%CI: 3.08-37.55; p

Background Extracorporeal membrane oxygenation (ECMO) is an effective cardiopulmonary support therapy, which can provide temporary cardiopulmonary support for critically ill patients whose condition cannot be reversed by conventional therapy. However, there are many complications in the use of ECMO, such as bleeding, thrombosis, and so on. Among them, inferior vena cava (IVC) thrombosis which can cause pulmonary embolism is a rare complication, which may be life-threatening. Case presentation A 75-year-old female patient (Han Chinese ethnicity) with acute heart failure due to acute myocardial infarction in our department was retrospectively analyzed. After regular treatment was unsuccessful, she was treated with venoarterial ECMO (VA-ECMO). After her condition improved, she was withdrawn from ECMO and experienced a complication of IVC thrombosis. Enoxaparin was given immediately for 1 mg/kg every 12 hours hypodermic injection. The thrombus disappeared after anticoagulant therapy. She was discharged on the 60th day. Her level of consciousness returned to normal without residual central nervous system-related complications. Conclusions IVC thrombosis is one of the possible serious complications in the process of ECMO therapy. Prevention of thrombosis and optimization of the anticoagulant regimen are the main preventive measures. Anticoagulant therapy is still the main treatment of IVC thrombosis in the process of ECMO therapy. Other interventional strategies need to accumulate clinical experience.

As an aberrant base in DNA, uracil is generated by dUMP misincorporation or cytosine deamination, and involved in multiple physiological and pathological processes. Current methods for whole-genome mapping of uracil all rely on uracil-DNA N-glycosylase (UNG) and are limited in resolution or specificity. Here, we present a UNG-independent Single-Nucleotide resolution Uracil Sequencing (SNU-seq) method utilizing the UdgX protein which specifically excises the uracil and forms a covalent bond with the resulting deoxyribose. SNU-seq was validated on synthetic DNA and applied to mammalian genomes. We found that the uracil content of pemetrexed-treated cells fluctuated along with DNA replication timing. We also accurately detected uracil introduced through cytosine deamination by the cytosine base editor (nCas9-APOBEC) and verified uracil occurrence in “WRC” motif within Activation-Induced Cytidine Deaminase (AID) hotspot regions in CSR-activated UNG−/− B cells.

The pathological mechanism underlying heat stroke (HS) is associated with the dysbalanced inflammation and coagulation cascade. Cell-derived circulating extracellular vesicles (EVs), as a novel pathway mediating intercellular communication, are associated with the immune response and inflammation in critical inflammatory syndromes, such as sepsis. Although these vesicles contain genetic material correlated with their biological function, their molecular cargo during HS remains unknown. In this study, we evaluate the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) associated with inflammatory responses and coagulation cascade in exosomes of patients with HS. Blood samples were collected from three patients with HS at the time of admission to the intensive care unit; three healthy volunteers were selected as control. Exosomes were isolated using ultracentrifugation, and their miRNA content was profiled using next-generation sequencing; mRNA content was evaluated using qPCR array. Compared with those from healthy volunteers, exosomes from patients with HS showed substantial changes in the expression of 202 exosomal miRNAs (154 upregulated and 48 downregulated miRNAs). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290, and let7-5p, whereas the most downregulated ones included miR-150-3p, 146a-5p, and 151a-3p. Gene ontology enrichment of the miRNAs of patients with HS compared with control subjects were associated mostly with inflammatory response, including T cell activation, B cell receptor signaling, dendritic cell chemotaxis and leukocyte migration, and platelet activation and blood coagulation. The identified miRNAs were primarily enriched to the signal transduction pathways namely, T cell receptor signaling, Ras signaling, chemokine signaling, platelet activation, and leukocyte transendothelial migration, all of which are associated with inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation, and platelet activation were further verified in serum exosomes. Exosomes from patients with HS convey miRNAs and mRNAs associated with pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during HS.

Objectives: The role of omega-3 fatty acids in the treatment of sepsis is always on paradox. we tried to retrieve and download the patients’ data in a certain period through the hospital information system, used data sorting so as to screen out the patients with sepsis so as to find out the role of omega-3 fatty acids in sepsis. Methods: Through the hospital information system, retrieve and include the patients who were admitted to the Department of critical medicine of Shenzhen People's Hospital from December 2016 to June 2019, screen out patients diagnosed with sepsis according to a certain criterion. The patients were grouped by whether they were applicated with omega-3 fatty acid or not. Results: A total of 1733 cases included into analysis, among of whom 303 cases were applicated with omega-3 fatty acid. The amounts and baseline conditions between both groups were imbalance. Severity of omega-3 fatty acid group was higher than that of control group. Chi-square test found that the mortality rate of omega-3 fatty acid was higher than that of control group (p < 0.0001). But age, gender, whether there is abdominal infection, whether there is septicemia, shock, the need for mechanical ventilation, and the need for renal replacement therapy may all affect the prognosis of the patients. If these factors were used as covariates, multiple logistic regression analysis showed that there was no significant difference in mortality rate between the treatment group and the control group (P = 0.574). Survival analysis showed that the survival rate of treatment group was higher than that of the control group when at the end of total treatment duration (P = 0.035). Conclusion: For patients with more severe sepsis, doctors are more likely to use omega-3 fatty acids in the early stage. Omega-3 fatty acids may improve the long-term prognosis of sepsis, but the conclusion still needs to be accepted carefully.

Background: The pathological mechanism of HS is associated with the dysbalanced inflammation and coagulation cascade. The cells-derived circulating extracellular vesicles (EVs) as a novel pathway mediating intercellular communication were evidenced to be associated with immune response and inflammation in critical inflammatory syndromes such as sepsis. Despite previous studies demonstrating that these vesicles contain genetic material related to their biological function, their molecular cargo during heat stroke is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and coagulation cascade in exosomes of patients with heat stroke. Methods: Blood samples were collected from 3 patients with heat stroke at ICU admission. Three healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, their miRNA content was profiled by next generation sequencing and mRNA content was evaluated by qRT-PCR array. Results: As compared with healthy volunteers, exosomes from patients with heat stroke had significant changes in 202 exosomal miRNAs (154 miRNAs upregulated and 48 downregulated). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290 and let7-5p whileas the most downregulated ones included miR-150-3p, 146a-5p and 151a-3p. The GO enrichment by the miRNAs of patients with heat stroke compared with control subjects were related mostly to inflammatory response including T cell activation, B cell receptor signaling, DC chemotaxis and leukocyte migration, and platelet activation and blood coagulation. KEGG pathway analysis determined those identified miRNAs were mainly enriched to the signal transduction pathways namely, T cell receptor signaling pathway, Ras signaling pathway, Chemokine signaling pathway, Platelet activation, and Leukocyte transendothelial migration. These pathways were mainly related to inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation and platelet activation were further verified in serum exosomes.Conclusions: Exosomes from patients with heat stroke convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during heat stroke.

BackgroundThe threat of antimicrobial resistance calls for more efforts in basic science, drug discovery, and clinical development, particularly gram-negative carbapenem-resistant pathogens.Objectives and methodsWhole-cell–based screening was performed to identify novel antibacterial agents against Acinetobacter baumannii ATCC19606. Spontaneously resistant mutant selection, whole-genome sequencing, and surface plasmon resonance were used for target identification and confirmation. Checkerboard titration assay was used for drug combination analysis.ResultsA small molecule named 6D1 with the chemical structure of 6-fluorobenzo[d]isothiazol-3(2H)-one was identified and exhibited activity against A. baumannii ATCC19606 strain (minimal inhibitory concentration, MIC = 1 mg/L). The mutation in the plasmid-derived ohrB gene that encodes a peroxidase was identified in spontaneously resistant mutants. Treatment of the bacteria with 6D1 resulted in increased sensitivity to peroxide such as tert-butyl hydroperoxide. The binding of 6D1 and OhrB was confirmed by surface plasmon resonance. Interestingly, the MIC of kanamycin against spontaneously resistant mutants decreased. Finally, we identified the effect of 6D1 on enhancing the antibacterial activity of kanamycin, including New Delhi metallo-β-lactamase (NDM-1)-producing carbapenem-resistant Klebsiella pneumoniae, but not in strains carrying kanamycin resistance genes.ConclusionsIn this study, we identified a peroxidase inhibitor that suppresses the growth of A. baumannii and enhances the antibacterial activity of kanamycin. We propose that peroxidase may be potentially used as a target for kanamycin adjuvant development.

Objectives: The role of omega-3 fatty acids in the treatment of sepsis is always on paradox. we tried to retrieve and download the patients’ data in a certain period through the hospital information system, used data sorting so as to screen out the patients with sepsis so as to find out the role of omega-3 fatty acids in sepsis.Methods: Through the hospital information system, retrieve and include the patients who were admitted to the Department of critical medicine of Shenzhen People's Hospital from December 2016 to June 2019, screen out patients diagnosed with sepsis according to a certain criterion. The patients were grouped by whether they were applicated with omega-3 fatty acid or not.Results: A total of 1733 cases included into analysis, among of whom 303 cases were applicated with omega-3 fatty acid. The amounts and baseline conditions between both groups were imbalance. Severity of omega-3 fatty acid group was higher than that of control group. Chi-square test found that the mortality rate of omega-3 fatty acid was higher than that of control group (p < 0.0001). But age, gender, whether there is abdominal infection, whether there is septicemia, shock, the need for mechanical ventilation, and the need for renal replacement therapy may all affect the prognosis of the patients. If these factors were used as covariates, multiple logistic regression analysis showed that there was no significant difference in mortality rate between the treatment group and the control group (P = 0.574). Survival analysis showed that the survival rate of treatment group was higher than that of the control group when at the end of total treatment duration (P = 0.035).Conclusion: For patients with more severe sepsis, doctors are more likely to use omega-3 fatty acids in the early stage. Omega-3 fatty acids may improve the long-term prognosis of sepsis, but the conclusion still needs to be accepted carefully.

Objectives The role of omega-3 fatty acids in the treatment of sepsis is always on paradox. we tried to retrieve and download the patients’ data in a certain period through the hospital information system, used data sorting so as to screen out the patients with sepsis so as to find out the role of omega-3 fatty acids in sepsis. Methods Through the hospital information system, retrieve and include the patients who were admitted to the Department of critical medicine of Shenzhen People's Hospital from December 2016 to June 2019, screen out patients diagnosed with sepsis according to a certain criterion. The patients were grouped by whether they were applicated with omega-3 fatty acid or not. Results A total of 1733 cases included into analysis, among of whom 303 cases were applicated with omega-3 fatty acid. The amounts and baseline conditions between both groups were imbalance. Severity of omega-3 fatty acid group was higher than that of control group. Chi-square test found that the mortality rate of omega-3 fatty acid was higher than that of control group (p < 0.0001). But age, gender, whether there is abdominal infection, whether there is septicemia, shock, the need for mechanical ventilation, and the need for renal replacement therapy may all affect the prognosis of the patients. If these factors were used as covariates, multiple logistic regression analysis showed that there was no significant difference in mortality rate between the treatment group and the control group (P = 0.574). Survival analysis showed that the survival rate of treatment group was higher than that of the control group when at the end of total treatment duration (P = 0.035). Conclusion For patients with more severe sepsis, doctors are more likely to use omega-3 fatty acids in the early stage. Omega-3 fatty acids may improve the long-term prognosis of sepsis, but the conclusion still needs to be accepted carefully.

BackgroundHypervirulent Klebsiella pneumoniae lacking classical virulence factors is uncommon, and the virulence mechanisms of this organism are not understood.MethodsFollowing a retrospective study of carbapenem-resistant K. pneumoniae based on core genome multilocus sequence typing (cgMLST), isolates that caused high mortality were investigated with a genome-wide association study (GWAS), proteome analysis and an animal model.ResultsThe sublineage of sequence type 11 (ST11) K. pneumoniae, which belongs to complex type 3176 (CT3176) and K-locus 47 (KL47), was highlighted due to the high mortality of infected patients. GWAS analysis showed that ampR was associated with the CT3176 isolates. In a mouse model, the mortality of ampR-carrying isolates was comparable to that of the typical hypervirulent isolate GM2. Even during the first 24 hours of infection, the bacterial load and pathological changes of the ampR-carrying isolates in the lungs were more severe than those of GM2. The ampR complement mutant was able to enhance the virulence of the KL47 isolate but not the virulence of KL1. Proteome analysis showed that the expression of WcaJ in the ampR+ isolates was significantly higher than that in the ampR− isolates, and this result was also confirmed by transcription tests and capsule staining. It is suggested that the enhancement of the initial stage of capsule synthesis may be the cause of the high virulence of these non-hypermucoviscous ST11 carbapenem-resistant K. pneumoniae isolates.ConclusionsNon-hypermucoviscous ST11 hypervirulent carbapenem-resistant K. pneumoniae warrants continued surveillance and investigation.

Additional file 1: Figure S1. Identification of co-expression modules for dataset GSE65682. A) Parameter setup. B) Gene dendrogram and module colors. C) Module dendrogram. Figure S2. Identification of co-expression modules for dataset GSE69528. A) Parameter setup. B) Gene dendrogram and module colors. C) Module dendrogram. Figure S3. Identification of co-expression modules from the topological overlap matrix using WGCNA for dataset GSE69528. Figure S4. Kaplan–Meier curves of two patient groups with higher or lower EG value for module 15, 23, 45, and 36, respectively. Figure S5. Example of the coexpression modules enriched of up (31 and 37) or down-regulated DEGs (45 and 39). Vertexes correspond to genes and edges correspond to expression correlation. Only the edges with the absolute value of PCC greater than 0.5 are shown. Up-regulated DEGs are colored in red while down-regulated DEGs are in blue.

Acinetobacter baumannii is an important human pathogen due to its multi-drug resistance, but is usually with low-grade virulence. Although a mouse model revealed different virulence grades of clinical carbapenem-resistant A. baumannii (CRAB) strains, the genetic basis remains unknown. We collected 61 CRAB isolates from intensive care unit of Shenzhen People’s Hospital (Shenzhen, China), and analyzed them used whole genome sequencing (WGS), multilocus sequence typing (MLST) and core genome MLST (cgMLST), transmission chain reconstruction and Comparative genomic tools. A mouse pneumonia model was used to confirm the hypervirulent phenotype. Eleven complex types (CT) were identified based on core genome multilocus sequence typing scheme. CT512 showed higher transmissibility and bloodstream infection rates than other CTs. A genomic region Lyb-2-4 was shared by CT512 and CT2092 but not CT2085. The mortality rates of patient infected with CRAB harboring Lyb-2-4 was significantly higher than those infected with CRAB isolates without Lyb-2-4 (77.8% vs 24.5%, p < 0.01). In the mouse model, the survival rates of strains containing the Lyb-2-4 region (LAC-4, 5122 and 2092) were significantly lower than for strains without Lyb-2-4 (7152, 71517, 20859 and ATCC17978). One open reading frame (ORF) was a marker for the presence of Lyb-2-4, and PCR of a segment of this ORF, designated as hvcT, served as a tag for hypervirulent CRAB. Our study should be very useful in advising the clinician to implement medical intervention earlier, and also making the worldwide surveillance of these hypervirulent CRAB strains easier.IMPORTANCEHypervirulent CRAB strains are expected to pose a threat to human health because infection of these strains is associated with high mortality and multidrug resistance. The rapid hypervirulent CRAB identification assay will facilitate prompt medical intervention. Our findings should provoke surveillance for hypervirulent CRAB strains harboring Lyb-2-4 in other countries. Further research should focus on the mechanism of hypervirulence, the acquisition of this genomic region and the development of control measures to prevent further dissemination.

Sex-determining region Y-box 9 (SOX9), a vital transcription factor, play important roles in numerous biological and pathological processes. However, the clinical significance and biological role of SOX9 expression has not been characterized in human esophageal squamous cell cancer (ESCC). Herein, we found that SOX9 was markedly upregulated, at both mRNA and protein level, in ESCC cell lines and ESCC tissues and that SOX9 expression was significantly correlated with tumor clinical stage, T classification, N classification, M classification, pathological differentiation, and shorter overall survival. The proliferation and tumorigenicity of ESCC cells were dramatically induced by SOX9 overexpression but were inhibited by SOX9 knockdown both in vitro and in vivo. Moreover, we demonstrated that upregulation of SOX9 increased the expression of phosphorylated Akt, the cyclin-dependent kinase (CDK) regulator cyclin D1, phosphorylated forkhead box O (FOXO)1, and phosphorylated FOXO3, but SOX9 downregulation decreased their expression, whereas the levels of the CDK inhibitors p21Cip1 and p27Kip1 were attenuated in SOX9-transduced cells. Taken together, our results suggest that SOX9 plays an important role in promoting the proliferation and tumorigenesis of ESCC and may represent a novel prognostic marker for the disease.

Objective This study aimed to investigate the possible effect of omega-3 fatty acids on reducing the mortality of sepsis and sepsis-induced acute respiratory distress syndrome (ARDS) in adults. Methods Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, WangFang database, and Chinese BioMedical Literature Database from their inception to March 6, 2017, were searched using systematic review researching methods. Five factors were analyzed to investigate the correlation between omega-3 fatty acids (either parenteral or enteral supplementation) and mortality rate. Results Forty randomized controlled trials (RCTs) were initially included, but only 25 of them assessed mortality. Of these RCTs, nine used enteral nutrition (EN) and 16 used parenteral nutrition (PN). The total mortality rate in the omega-3 fatty acid group was lower than that in the control group. However, the odds ratio (OR) value was not significantly different in the EN or PN subgroup. Eighteen RCTs including 1790 patients with similar severity of sepsis and ARDS were also analyzed. The OR value was not significantly different in the EN or PN subgroup. Omega-3 fatty acids did not show positive effect on improving mortality of sepsis-induced ARDS (p = 0.39). But in EN subgroup, omega-3 fatty acids treatment seemed to have some benefits in reducing mortality rate (p = 0.04). In the RCTs including similar baseline patients, partial correlation analysis found that the concentration ratio of n-6 to n-3 fatty acids had positive correlation with reduction of mortality (RM) (γ = 0.60, P = 0.02), whereas the total number of each RCT had negative correlation with RM (γ = − 0.54, P = 0.05). Conclusions This review found that omega-3 fatty acid supplementation could reduce the mortality rate of sepsis and sepsis-induced ARDS. However, further investigation based on suitable concentrations and indications is needed to support the findings.

HuaiSheng Chen,1,* HuaDong Zhang,1,* Wei Li,1 ShengNan Wu,1 Wei Wang2 1Intensive Care Unit, 2Endocrinology Department, Second Affiliated Hospital of Jinan University, Shenzhen People’s Hospital, Shenzhen, People’sRepublic of China *These authors contributed equally tothis work Background: Acute gastrointestinal injury (AGI) is a common problem in the intensive care unit (ICU). This study is a review of the gastrointestinal function of patients in critical care, with the aim to assess the feasibility and effectiveness of grading criteria developed by the European Society of Intensive Care Medicine (ESICM) Working Group on Abdominal Problems (WGAP). Methods: Data of patients who were admitted to the ICU of Shenzhen People’s Hospital, Shenzhen, People’s Republic of China, from January 2010 to December 2011 were reviewed. A total of 874 patients were included into the current study. Their sex, age, ICU admissive causes, complication of diabetes, AGI grade, primary or secondary AGI, mechanical ventilation (MV), and length of ICU stay (days) were recorded as risk factors of death. These risk factors were studied by unconditioned logistic regression analysis. Results: All the risk factors affected mortality rate. Unconditional logistic regression analysis revealed that the mortality rate of secondary AGI was 71 times higher than primary AGI (odds ratio [OR] 4.335, 95% CI [1.652, 11.375]). When the age increased by one year, the mortality probability would increase fourfold. Mortality in patients with MV was 63-fold higher than for patients with non-MV. Mortality rate increased 0.978 times with each additional day of ICU stay. Conclusion: Secondary AGI caused by severe systemic conditions can result in worsened clinical outcomes. The 2012 ESICM WGAP AGI recommendations were to some extent feasible and effective in guiding clinical practices, but the grading system lacked the support of objective laboratory outcomes. Keywords: critical care, acute gastrointestinal injury, mortality

To observe change of iliac artery SMC collagen fiber after balloon injury in tanshinone II A treatment group.Thirty male pure breed New Zealand white rabbits were underwent experimental balloon injury in left iliac artery. Then the rabbits were assigned into treatment group (n = 15) and control group (n = 15). Tanshinone II A sulfonic acid natrium was injected intravenously in treatment group. Saline was venously injected in control group. The balloon injured arteries were harvested in the 7th, 14th, and 28th days after surgery.Analysis of Collagen fibers staining found that a weak positive staining was shown at the 7th day post-operation in both groups,while a strong positive result was seen at the 14th day in control group. Positive results were even shown at the 14th day in treatment group,but less strong than that of the control. At the 28th day post-operation, collagen fiber staining become weak in treatment group, but increased in the control. Difference between both group in the 28th day post-operation was significant (P = 0.017). Time-dependence tendency of collagen fiber changing was statistically significant (P = 0.005).Tanshinone II A suppress stack of extracellular matrix after balloon injury so as to prevent restenosis.