Publications by authors named "Xiaochun Ma"

144 Publications

Integrative Bioinformatics Analysis Revealed Mitochondrial Defects Underlying Hypoplastic Left Heart Syndrome.

Int J Gen Med 2021 14;14:9747-9760. Epub 2021 Dec 14.

Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.

Background: Hypoplastic left heart syndrome (HLHS) is one of the most complex congenital cardiac malformations, and the molecular mechanism of heart failure (HF) in HLHS is still elusive.

Methods: Integrative bioinformatics analysis was performed to unravel the underlying genes and mechanisms involved in HF in HLHS. Microarray dataset GSE23959 was screened out for the differentially expressed genes (DEGs), after which the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were carried out using the Metascape. The protein-protein interaction (PPI) network was generated, and the modules and hub genes were identified with the Cytoscape-plugin. And the integrated network of transcription factor (TF)-DEGs and miRNA-DEGs was constructed, respectively.

Results: A total of 210 DEGs were identified, including 135 up-regulated and 75 down-regulated genes. The functional enrichment analysis of DEGs pointed towards the mitochondrial-related biological processes, cellular components, molecular functions and signaling pathways. A PPI network was constructed including 155 nodes as well as 363 edges. And 15 hub genes, such as , were identified based on three topological analysis methods and mitochondrial components and functions were the most relevant. Furthermore, by integrating network interaction construction, 23 TFs (NFKB1, RELA, HIF1A, VHL, GATA1, PPAR-γ, etc.) as well as several miRNAs (hsa-miR-155-5p, hsa-miR-191-5p, hsa-mir-124-3p, hsa-miR-1-3p, etc.) were detected and indicated the possible involvement of NF-κB signaling pathways in mitochondrial dysfunction in HLHS.

Conclusion: The present study applied the integrative bioinformatics analysis and revealed the mitochondrial-related key genes, regulatory pathways, TFs and miRNAs underlying the HF in HLHS, which improved the understanding of disease mechanisms and the development of novel therapeutic targets.
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http://dx.doi.org/10.2147/IJGM.S345921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8684406PMC
December 2021

Utilizing reclassification to explore characteristics and prognosis of KDIGO AKI subgroups: a retrospective analysis of a multicenter prospective cohort study.

Ren Fail 2021 Dec;43(1):1569-1576

Medical Intensive Care Unit, Peking Union Medical College Hospital, Beijing, China.

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 (Scr), no significant differences were observed in ICU mortality (=0.076, =0.070) or renal replacement therapy (RRT) ratio, (=0.356, =0.471) between stage 1a and 1b, but stage 1b had longer ICU length of stay (LOS) than stage 1a (<0.001, =0.032). In the Kaplan-Meier survival analysis, no differences were observed in ICU mortality between stage 1a and 1b (=0.378, =0.255). In a multivariate analysis, respiratory failure [HR = 4.462 (95% CI 1.144-17.401),  = 0.031] and vasoactive drug therapy [HR = 4.023 (95% CI 1.584-10.216),  = 0.003] were found to be independently associated with increased risk of death.

Conclusion: ICU LOS benefit was more prominent in KDIGO AKI stage 1a patients than in stage 1 b. Further prospective studies with a larger sample size are necessary to confirm the effectiveness of reclassification.
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http://dx.doi.org/10.1080/0886022X.2021.1997761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648037PMC
December 2021

Unfractionated Heparin Attenuated Histone-Induced Pulmonary Syndecan-1 Degradation in Mice: a Preliminary Study on the Roles of Heparinase Pathway.

Inflammation 2021 Oct 16. Epub 2021 Oct 16.

Department of Critical Care Medicine, the First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang, 110001, Liaoning Province, People's Republic of China.

Endothelial glycocalyx degradation is thought to facilitate the development of sepsis. Histone is a significant mediator in sepsis. Unfractionated heparin (UFH) possessed beneficial effects on sepsis. Thereby, this study aims to figure out whether histone can disrupt glycocalyx and to investigate the protective effect and mechanism of UFH. Male mice (C57BL/6, 8-10 weeks old, weighing 20-25 g) were randomly divided into five groups including control group, histone group, histone + UFH group, histone + heparinase (HPA) inhibitor group, and histone + UFH + HPA inhibitor group. The mice were treated with histone (50 mg/kg) via tail vein immediately after HPA (20 mg/kg) injection. UFH (400 U/kg) was injected 1h after histone administration. The other groups were injected with equal volume of sterile saline accordingly. UFH alleviated histone-induced lung injury and pulmonary edema. UFH inhibited histone-induced lung coagulation activation and inflammatory response. UFH treatment markedly inhibited pulmonary glycocalyx degradation by reducing the histone-induced decrease in the levels of lung syndecan-1 mRNA and protein. UFH downregulated histone-induced expression of HPA mRNA and protein, and thus alleviated glycocalyx degradation. UFH protects against histone-induced pulmonary glycocalyx injury partly by heparinase pathway.
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http://dx.doi.org/10.1007/s10753-021-01578-wDOI Listing
October 2021

Immune checkpoint molecule TIGIT manipulates T cell dysfunction in septic patients.

Int Immunopharmacol 2021 Dec 13;101(Pt B):108205. Epub 2021 Oct 13.

Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, China. Electronic address:

Sepsis is a dysregulated host response to infection. T cell dysfunction results in the failure to eradicate pathogens and the increased susceptibility to nosocomial infections and mortality during sepsis. Although PD-1 has shown to be a promising target to interfere with T cells dysfunction, the role of other coinhibitory receptors in sepsis remains largely elusive. Here we demonstrated that the immune checkpoint molecule TIGIT on lymphocytes and the critical role of TIGIT in regulating T cell responses in sepsis. Fifty septic patients and seventeen healthy donors were prospectively enrolled. The expression patterns of TIGIT and other molecules on lymphocytes were quantitated by flow cytometry. Ex vivo functional assays were also conducted. Results show that TIGIT expression on T cells was significantly upregulated in sepsis and septic shock patients relative to healthy donors. Elevated frequencies of TIGIT T cells correlated with aggravated inflammatory response and organ injuries. Of note, TIGIT expression on CD8 T cells showed a competitive capability to predict ICU mortality in sepsis. TIGIT T cells expressed higher levels of PD-1, lower levels of CD226, and released fewer cytokines. Strikingly, ex vivo blockade of TIGIT using anti-TIGIT antibody restored the frequencies of cytokine-producing T cells from septic patients. These data illustrate that TIGIT on T cells is being used not only as a clinical predictor of poor prognosis but also as a potential target of novel immunotherapeutic intervention during sepsis.
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http://dx.doi.org/10.1016/j.intimp.2021.108205DOI Listing
December 2021

Protective effect of cynaroside on sepsis-induced multiple organ injury through Nrf2/HO-1-dependent macrophage polarization.

Eur J Pharmacol 2021 Nov 22;911:174522. Epub 2021 Sep 22.

School of Life Science, Zhejiang Chinese Medical University, 310053, Hangzhou, China. Electronic address:

Cynaroside is the primary flavonoid component of honeysuckle which has been widely used as Chinese traditional medicine given its anti-inflammation properties. Overactive systemic inflammatory response and multi-organ injury are the leading causes of life-threatening sepsis. Regulation of macrophage polarization balance may act as a promising strategy for its treatment. In the present study, we aimed to investigate whether cynaroside exerted protective effects against sepsis and its potential mechanism. Building upon a sepsis mouse model, we observed cynaroside alleviated serum levels of inflammatory factors including IL-1β and TNF-α at 5 and 10 mg/kg. The pathological injury of heart, kidney and lung was remarkedly attenuated as the levels of blood urea nitrogen, creatinine, creatine kinase-MB and lactate dehydrogenase were reduced nearly 2.8-, 2.7-, 2.4-, and 2.5-fold as compared with the sepsis mice, respectively. We further demonstrated cynaroside suppressed the biomarker of pro-inflammatory macrophage M1 phenotype (iNOS+) and promotes the anti-inflammatory M2 polarization (CD206+) in the injury organs of septic mice. Mechanistic research verified cynaroside inhibited LPS-induced polarization of macrophage into M1 phenotype, which can be highly blocked by Nrf2 inhibitor. Expectedly, Nrf2 and its downstream (Heme oxygenase-1 (HO-1)) was upregulated in injury organs after treating with cynaroside, indicating the involvement of Nrf2 signaling. Taken together, the data claims cynaroside ameliorated systematic inflammation and multi-organ injury dependent on Nrf2/HO-1 pathway in septic mice.
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http://dx.doi.org/10.1016/j.ejphar.2021.174522DOI Listing
November 2021

The Predictive Role of Lymphocyte-to-Monocyte Ratio in Acute Kidney Injury in Acute Debakey Type I Aortic Dissection.

Front Surg 2021 11;8:704345. Epub 2021 Aug 11.

Department of Cardiovascular Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

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. 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. 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. LMR is an independent prognostic indicator incorporated into the predictive model with other risk factors to predict the post-operative AKI in ADTIAD.
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http://dx.doi.org/10.3389/fsurg.2021.704345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384963PMC
August 2021

Surgical Intervention of a Rare Case of Complex Coarctation of Descending Aorta.

Circ Cardiovasc Imaging 2021 10 27;14(10):e013010. Epub 2021 Aug 27.

Department of Cardiovascular Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China (H.S., J.H., D.Z., S.C., S.Z., Z.W., C.Z., H.Z., X.M.).

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http://dx.doi.org/10.1161/CIRCIMAGING.121.013010DOI Listing
October 2021

[Clinical value of neutrophil/lymphocyte ratio in early prediction of the incidence of organ dysfunction and 28-day mortality in patients with sepsis].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jun;33(6):665-670

Department of Critical Care Medicine, the First Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning, China. Corresponding author: Zhang Zhidan, Email:

Objective: To evaluate the clinical value of neutrophil/lymphocyte ratio (NLR) in early prediction of the incidence of sepsis-induced organ dysfunction and 28-day mortality.

Methods: A retrospective study was conducted in 815 adult patients with sepsis admitted to the department of critical care medicine of the First Affiliated Hospital of China Medical University from January 2017 to December 2019. The clinical data including age, gender and complication were collected, and the peripheral blood routine indexes at 24, 48 and 72 hours after the diagnosis of sepsis were collected, and the NLR was calculated. The primary endpoint of the study was the incidences of sepsis related acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) and acute liver failure (ALF); the secondary endpoint was the 28-day in-hospital mortality in septic patients with organ dysfunction. Univariate and multivariate Logistic regression were used to analyze the risk factors of organ dysfunction and 28-day mortality in patients with sepsis, the receiver operating characteristic curve (ROC curve) was drawn and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of NLR for organ dysfunction and 28-day mortality in patients with sepsis.

Results: A total of 714 patients with sepsis were enrolled for final statistical analysis. There was no significant difference in NLR at 24, 48 and 72 hours in patients with or without organ dysfunction (such as AKI, ARDS, DIC and ALF). Logistic regression analysis showed that there was no significant difference in NLR at 24 hours with 28-day in-hospital mortality [odds ratio (OR) = 1.006, 95% confidence interval (95%CI) was 0.994-1.019, P = 0.323]. However, NLR at 48 hours and 72 hours had a significant difference with 28-day mortality (48 hours: OR = 1.026, 95%CI was 1.013-1.040, P = 0.000; 72 hours: OR = 1.021, 95%CI was 1.005-1.037, P = 0.010), which suggested that NLR at 48 hours and 72 hours after diagnosis were independent risks factor for 28-day mortality in patients with sepsis. ROC curve showed that the AUC of NLR at 48 hours was 0.598, 95%CI was 0.540-0.658, P = 0.02; when the cut-off value was 10.1, the sensitivity and specificity for predicting 28-day mortality was 75.2% and 58.0%, respectively; the AUC of NLR at 72 hours was 0.595, 95%CI was 0.536-0.655, P = 0.03; when the cut-off value was 9.24, the sensitivity and specificity for predicting 28-day mortality was 75.3% and 59.9%, respectively.

Conclusions: NLR cannot predict the occurrence of AKI, ARDS, DIC and ALF in sepsis in early stage. NLR has a certain clinical value in predicting 28-day mortality in patients with sepsis, but its predictive efficiency is low.
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http://dx.doi.org/10.3760/cma.j.cn121430-20210325-00437DOI Listing
June 2021

Unfractionated Heparin Improves the Intestinal Microcirculation in a Canine Septic Shock Model.

Mediators Inflamm 2021 23;2021:9985397. Epub 2021 Jun 23.

Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

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 , (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 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: 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.
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http://dx.doi.org/10.1155/2021/9985397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245220PMC
January 2022

Differences in the reaction of hyperlipidemia on different endothelial progenitor cells based on sex.

Biomed Rep 2021 Aug 7;15(2):64. Epub 2021 Jun 7.

Department of Cardiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.

The sex of a patient can affect the outcomes of several cardiovascular diseases, and men generally tend to experience earlier episodes of cardiovascular diseases compared with women. The progression of atherosclerosis during hyperlipidemia can be induced by reactive oxygen species (ROS) and oxidized-low-density lipoprotein (ox-LDL). By contrast, bone marrow (BM)-derived endothelial progenitor cells (EPCs) have been reported to serve a protective role against atherosclerosis. The aim of the present was to compare the effects of sex under conditions of hyperlipidemia on different populations of EPCs, and to identify the potential underlying mechanisms. EPC numbers and ROS levels in the blood and BM were measured using fluorescence activated cell sorting in male and female LDL receptor knock-out C57BL/6 mice maintained on a high-fat diet for 6 months, and in male and female wild type C57BL/6 mice following ox-LDL injection for 3 days. Female hyperlipidemic mice exhibited lower levels of plasma lipids, atherosclerotic plaque formation, intracellular EPC ROS formation and inflammatory cytokine levels. Furthermore, BM CD34/ fetal liver kinase-1 (Flk-1), CD34/CD133 and stem cell antigen-1/Flk-1, as well as all circulating EPCs, were maintained at higher levels in female hyperlipidemic mice. In addition, similar changes with regards to BM CD34/Flk-1, CD34/CD133, c-Kit/CD31 and circulating CD34/Flk1 and CD34/CD133 EPCs were observed in female mice following ox-LDL treatment. These sustained higher levels of BM and circulating EPCs in female mice with hyperlipidemia may be associated with reduced levels of ox-LDL as a result of reduced intracellular ROS formation in EPCs and decreased inflammatory cytokine production.
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http://dx.doi.org/10.3892/br.2021.1440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212447PMC
August 2021

Multiplexed quantitative evaluation on mitochondrial toxicity of tris (2,3-dibromopropyl) phosphate in hepatocyte.

Ecotoxicol Environ Saf 2021 Sep 16;221:112425. Epub 2021 Jun 16.

Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, People's Republic of China; School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, People's Republic of China. Electronic address:

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 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 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.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112425DOI Listing
September 2021

Genomic epidemiology of in a general hospital in Shenyang, China: a three-year surveillance study.

Emerg Microbes Infect 2021 Dec;10(1):1088-1096

National Clinical Research Center for Laboratory Medicine & Department of Laboratory Medicine, the First Hospital of China Medical University, Shenyang, People's Republic of China.

is an emerging pathogenic fungal species found worldwide. Since April 2016, 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 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 isolates, including 92 clinical isolates and 1 environmental screening isolate were identified. Among the investigated wards, the 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 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 found in Shenyang and could also contribute to improve the understanding of the epidemiological characteristics of worldwide.
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http://dx.doi.org/10.1080/22221751.2021.1934557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183536PMC
December 2021

Traumatic mitral annular avulsion and interventricular septum dissection.

Cardiol Young 2021 Jun 12;31(6):1034-1035. Epub 2021 Mar 12.

Department of Cardiovascular Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China.

We presented a rare case of traumatic mitral annular avulsion and interventricular septum dissection after an unintentional falling injury in a 5-year-old female child. A successful surgical repair of mitral annulus and interventricular septum was performed to restore the haemodynamic stability.
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http://dx.doi.org/10.1017/S1047951121000044DOI Listing
June 2021

Elevated Secretion of Aldosterone Increases TG/HDL-C Ratio and Potentiates The Ox-LDL-Induced Dysfunction of HUVEC.

Cell J 2021 Apr 1;23(1):61-69. Epub 2021 Mar 1.

Department of Cell Biology, School of Life Sciences, Central South University, Changsha, Hunan, China.

Objective: Atherosclerosis (AS) is one of the most common causes of human death and disability. This study is designed to investigate the roles of aldosterone (Aldo) and oxidized low-density lipoprotein (Ox-LDL) in this disease by clinical data and cell model.

Materials And Methods: In this experimental study, clinical data were collected to investigate the Aldo role for the patients with primary aldosteronism or adrenal tumors. Cell viability assay, fluorescence-activated cell sorting (FACS) assay, apoptosis assay, cell aging analysis, and matrigel tube formation assay were performed to detect effects on human umbilical vein endothelial cells (HUVECs) treated with Aldo and/or Ox-LDL. Quantitative polymerase chain reaction (qPCR) and Western blot analysis were performed to figure out critical genes in the process of endothelial cells dysfunction induced by Aldo and/or Ox-LDL.

Results: We found that the Aldo level had a positive correlation with the TG/HDL-C ratio. Endothelial cell growth, angiogenesis, senescence, and apoptosis were significantly affected, and eNOS/Sirt1, the value of Bcl-2/Bax and Angiopoietin1/2 were significantly affected when cells were co-treated by Aldo and Ox-LDL.

Conclusion: Elevated Aldo with high Ox-LDL together may accelerate the dysfunction of HUVEC, and the Ox-LDL, especially for those patients with high Aldo should be well controlled. The assessment of the role of Aldo may provide a theoretical basis for the effective prevention and investigation of a new treatment of AS.
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http://dx.doi.org/10.22074/cellj.2021.7033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944123PMC
April 2021

Identification of Cleavage Sites Proteolytically Processed by NS2B-NS3 Protease in Polyprotein of Japanese Encephalitis Virus.

Pathogens 2021 Jan 21;10(2). Epub 2021 Jan 21.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.

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 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.
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http://dx.doi.org/10.3390/pathogens10020102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911949PMC
January 2021

Persistently higher serum sCD40L levels are associated with outcome in septic patients.

BMC Anesthesiol 2021 01 22;21(1):26. Epub 2021 Jan 22.

Department of Critical Care Medicine, The First Hospital of China Medical University, North Nanjing Street 155, Shenyang, 110001, Liaoning Province, China.

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, PaO/FiO 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.
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http://dx.doi.org/10.1186/s12871-021-01241-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820820PMC
January 2021

The Prevalence, Risk Factors, and Outcomes of Sepsis in Critically Ill Patients in China: A Multicenter Prospective Cohort Study.

Front Med (Lausanne) 2020 17;7:593808. Epub 2020 Dec 17.

Department of Critical Care Medicine, Fuxing Hospital, Capital Medical University, Beijing, China.

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. 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. 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. 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.
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http://dx.doi.org/10.3389/fmed.2020.593808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774866PMC
December 2020

Mosquito defensin facilitates Japanese encephalitis virus infection by downregulating the C6/36 cell-surface antiviral protein HSC70B.

Vet Microbiol 2021 Feb 28;253:108971. Epub 2020 Dec 28.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, No. 518, Ziyue Road, Shanghai, 200241, PR China. Electronic address:

Japanese encephalitis virus (JEV) is a viral zoonosis that can cause viral encephalitis, death and disability whose primary vector is the Culex mosquito. Viral infection induces a series of antimicrobial peptide responses in mosquitoes, and the effector defensin enhances JEV replication in mosquitoes. However, the underlying mechanisms by which defensin enhances JEV are not fully understood. Here, we found that mosquito defensin could downregulate the antiviral protein HSC70B and enhance virus infection in mosquitoes. The cell-surface protein HSC70B was significantly downregulated by JEV infection and defensin treatment. Low levels of HSC70B were beneficial to JEV infection in mosquitoes. Taken together, these findings show that defensin and HSC70B axis facilitates JEV infection in the mosquito.
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http://dx.doi.org/10.1016/j.vetmic.2020.108971DOI Listing
February 2021

Diagnosis and Management of Intraabdominal Infection: Guidelines by the Chinese Society of Surgical Infection and Intensive Care and the Chinese College of Gastrointestinal Fistula Surgeons.

Clin Infect Dis 2020 12;71(Suppl 4):S337-S362

Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

The Chinese guidelines for IAI presented here were developed by a panel that included experts from the fields of surgery, critical care, microbiology, infection control, pharmacology, and evidence-based medicine. All questions were structured in population, intervention, comparison, and outcomes format, and evidence profiles were generated. Recommendations were generated following the principles of the Grading of Recommendations Assessment, Development, and Evaluation system or Best Practice Statement (BPS), when applicable. The final guidelines include 45 graded recommendations and 17 BPSs, including the classification of disease severity, diagnosis, source control, antimicrobial therapy, microbiologic evaluation, nutritional therapy, other supportive therapies, diagnosis and management of specific IAIs, and recognition and management of source control failure. Recommendations on fluid resuscitation and organ support therapy could not be formulated and thus were not included. Accordingly, additional high-quality clinical studies should be performed in the future to address the clinicians' concerns.
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http://dx.doi.org/10.1093/cid/ciaa1513DOI Listing
December 2020

Adaptation of a live-attenuated genotype I Japanese encephalitis virus to vero cells is associated with mutations in structural protein genes.

Virus Res 2021 01 4;292:198256. Epub 2020 Dec 4.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China. Electronic address:

The SD12-F120 is a live-attenuated genotype I strain of Japanese encephalitis virus (JEV) and was obtained by serial passage of wild-type strain SD12 on BHK-21 cells combined with multiple plaque purification and virulence selection in mice. The large scale production and vast clinical trials always demand ideal safety and efficacy profile of live-attenuated vaccines. In the present study, SD12-F120VC has undergone serial passaging of P1-P30 in WHO qualified Vero cells to assess the potential effect of adaptation to growth on Vero cells. The series of experiments showed that vaccine SD12-F120VC (Vero cell adapted) variants have consistently increased in peak virus titer compared to early passages and have good adaptation to growth in Vero cells. The animal experiments showed that Vero cell adapted SD12-F120VC variants have attenuation phenotype in suckling mice and the plaque morphology for all SD12-F120VC variants was small. Vaccination of mice with SD12-F120VC vaccine produced complete protection for homologous SD12 genotype I strain, but failed to give the complete protection of vaccinated mice against the challenge of heterologous N28 genotype III strain. In response to immunization of SD12-F120VC in mice, the neutralizing antibodies titer against homologous SD12-F120VC and SD12 (GI) was higher than heterologous N28 (GIII) strain. The prM protein has 6 amino acid substitutions, of which 5 amino acid changes were confined at the start of the pr domain in the ∼40 amino acids, and some mutations in the pr domain of prM might contribute to Vero cell adaptation. Our findings in this study are important for validation, evaluation and quality control study of live attenuated flaviviruses vaccines and show that Vero cells are a suitable substrate for the production of a safe and stable live-attenuated JEV vaccine.
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http://dx.doi.org/10.1016/j.virusres.2020.198256DOI Listing
January 2021

Circular RNA-DENND4C in H9c2 cells relieves OGD/R-induced injury by down regulation of microRNA-320.

Cell Cycle 2020 11 22;19(22):3074-3085. Epub 2020 Oct 22.

Department of Cardiac Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University , Jinan, China.

Ischemic heart disease (IHD) is one of the most deadly diseases worldwide. To detect the regulatory mechanism, the circular RNA (circRNA)-differentially expressed in normal cells and neoplasia domain containing 4 C (DENND4C) was explored in the H9c2 cells. The circRNA-DENND4C overexpressing plasmid, si-circRNA-DENND4C and miR-320 mimic were transfected into the H9c2 cells and treated with OGD/R stimulation. We took CCK-8 method, Annexin V-FITC/PI-flow cytometer to search for viability and apoptotic ability. With the help of qRT-PCR and western blot, the expression of circRNA-DENND4C and miR-320, as well as the Bax, Cleaved PARP/caspase 3 and signal proteins were separately determined. Regulation of circRNA-DENND4C and miR-320 was confirmed by dual-luciferase reporter assay. OGD/R induced suppression of cell viability, but enhancement of apoptosis and block of ERK and mTOR pathways. Moreover, circRNA-DENND4C was up-regulated after OGD/R stimulation and augmented OGD/R-stimulated damage while circRNA-DENND4C silencing displayed opposite influences. miR-320 was negatively controlled and targeted by the circRNA-DENND4C.The overexpressed miR-320 impeded the effects of circRNA-DENND4C. Besides, circRNA-DENND4C relieved the suppression of ERK and mTOR pathways caused by OGD/R stimulation, and all promoting impacts of circRNA-DENND4C were reversed by the miR-320 mimic. Overexpressed circRNA-DENND4C in H9c2 cells attenuated OGD/R-induced injuries by the down-regulation of miR-320 through the ERK and mTOR activation.
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http://dx.doi.org/10.1080/15384101.2020.1831253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714513PMC
November 2020

Lymphocyte-to-monocyte ratio in predicting the calcific aortic valve stenosis in a Chinese case-control study.

Biomark Med 2020 10 16;14(14):1329-1339. Epub 2020 Oct 16.

Department of Cardiovascular Surgery, Shandong Provincial Hospital affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, Shandong 250021, China.

This study examined the role of lymphocyte-to-monocyte ratio (LMR), an inflammatory biomarker, in predicting the severity of calcific aortic valve stenosis (CAVS) in a Chinese case-control study. The LMR significantly decreased in the patients with CAVS compared with healthy controls. An inverse correlation was observed between the severity of stenosis and LMR in the patients. Additionally, the LMR was identified in the multivariate analysis as an independent predictor of severe CAVS. This study provides evidence of an inverse correlation between the severity of CAVS and LMR. LMR could potentially be applied as an independent predictor of severe CAVS and could be incorporated into a novel predictive model.
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http://dx.doi.org/10.2217/bmm-2020-0228DOI Listing
October 2020

Knockdown of circular RNA circMAT2B reduces oxygen-glucose deprivation-induced inflammatory injury in H9c2 cells through up-regulating miR-133.

Cell Cycle 2020 10 8;19(20):2622-2630. Epub 2020 Sep 8.

Department of Cardiac Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University , Jinan, Shandong, China.

Myocardial infarction (MI) is the main cause of morbidity and mortality. Reperfusion ways can cause damage to cardiomyocytes. CircMAT2B, a novel circRNA, takes positive roles in regulating glucose metabolism under hypoxia. Therefore, we aimed to explore the effects of circMAT2B on MI. Oxygen-glucose deprivation (OGD)-induced H9c2 cell model was employed to stimulate MI. Ex-circMAT2B, si-circMAT2B, miR-133 inhibitor and relative control were transfected into H9c2 cells. qRT-PCR was employed to examine levels of circMAT2B and miR-133. Cell activity, apoptosis, ROS generation and release of inflammatory factors were assessed by CCK-8, flow cytometry, ROS species assay kit and ELISA, respectively. Moreover, the expression of apoptosis-related and pathway-related factors was detected through western blot analysis. The results showed that circMAT2B expression was notably up-regulated by OGD treatment. Moreover, circMAT2B knockdown could effectively decrease OGD-induced the increasing of apoptosis, ROS generation and the expression of IL-1β, IL-6 and TNF-α. Besides, miR-133 was positively regulated by si-circMAT2B. CircMAT2B knockdown attenuated OGD-induced H9c2 cell damage and alleviated OGD-induced the inhibition of PI3K/AKT and Raf/MEK/ERK pathways through up-regulating miR-133. In brief, circMAT2B knockdown works as an inflammatory inhibitor in OGD-induced H9c2 cells inflammatory injury through up-regulating miR-133.
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http://dx.doi.org/10.1080/15384101.2020.1814025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644149PMC
October 2020

NS5-V372A and NS5-H386Y variations are responsible for differences in interferon α/β induction and co-contribute to the replication advantage of Japanese encephalitis virus genotype I over genotype III in ducklings.

PLoS Pathog 2020 09 3;16(9):e1008773. Epub 2020 Sep 3.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, P.R. China.

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.
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http://dx.doi.org/10.1371/journal.ppat.1008773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494076PMC
September 2020

Risk factors analysis of acute kidney injury following open thoracic aortic surgery in the patients with or without acute aortic syndrome: a retrospective study.

J Cardiothorac Surg 2020 Aug 7;15(1):213. Epub 2020 Aug 7.

Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong First Medical University, No.324 Jingwu Road, Jinan, 250021, Shandong, China.

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 < 0.001) were identified as independent predictors of postoperative AKI for the overall cohort; CPB time (OR 1.020, 95% CI: [1.009-1.031], p < 0.001) and preoperative LMR (OR 0.823, 95% CI: [0.701-0.966], p = 0.02) as independent predictors for the patients with AAS; age (OR 1.045, 95% CI: [1.015-1.076], p = 0.003), preoperative platelet (OR 0.993, 95% CI: [0.988-0.998], p = 0.04) and operation time (OR 1.496, 95% CI: [1.166-1.918], p = 0.002) as independent predictors for the patients without AAS.

Conclusions: The patients with AAS carry a higher risk for postoperative AKI compared with those without AAS. The predictive factors for postoperative AKI after OTAS are different for AAS- and non-AAS subgroups and operation time, CPB time and preoperative platelet are modifiable predictors of AKI.
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http://dx.doi.org/10.1186/s13019-020-01257-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412815PMC
August 2020

Extracorporeal Membrane Oxygenation (ECMO) in Critically Ill Patients with Coronavirus Disease 2019 (COVID-19) Pneumonia and Acute Respiratory Distress Syndrome (ARDS).

Med Sci Monit 2020 Aug 6;26:e925364. Epub 2020 Aug 6.

Department of Intensive Care Unit, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China (mainland).

Traced back to December 2019, an unexpected outbreak of a highly contagious new coronavirus pneumonia (COVID-19) has rapidly swept around China and the globe. There have now been an estimated 2 580 000 infections and more than 170 000 fatal cases around the world. The World Health Organization (WHO) estimated that approximately 14% of infections developed into severe disease, 5% were critically ill, and the mortality rate of critically ill patients is reported to be over 50%. The shortage of specific anti-viral treatment and vaccines remains a huge challenge. In COVID-19, refractory hypoxemia is common among the critically ill with acute respiratory distress syndrome (ARDS) despite invasive mechanical ventilation, and is further complicated by respiratory and circulatory failure. This difficult situation calls for the use of extracorporeal membrane oxygenation (ECMO) for assisting respiration and circulation if necessary. This article reviews the pertinent clinical literature, technical guidance, and expert recommendations on use of ECMO in critically ill cases of COVID-19. Here, we present basic knowledge and opinions about COVID-19 and ECMO, review the evidence on ECMO use in Middle East Respiratory Syndrome (MERS) and H1N1 influenza, share the technical guidance and recommendations on use of ECMO in COVID-19, summarize the current use of ECMO against COVID-19 in China, and discuss the issues in use of ECMO in COVID-19.
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http://dx.doi.org/10.12659/MSM.925364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430351PMC
August 2020

Risk of invasive candidiasis with prolonged duration of ICU stay: a systematic review and meta-analysis.

BMJ Open 2020 07 12;10(7):e036452. Epub 2020 Jul 12.

Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, China

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<0.001), between patients with and without . Meta-regression analysis found that South American patients had longer duration of ICU admission prior to candidaemia onset than patients elsewhere, while those in Asia had the shortest duration.

Conclusions: Patients with IC are associated with longer ICU stay, with the shortest duration of ICU admission prior to the candidaemia onset in Asia. This shows a more proactive strategy in the diagnosis of IC should be considered in caring for ICU patients.
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http://dx.doi.org/10.1136/bmjopen-2019-036452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359383PMC
July 2020

Detection of Japanese encephalitis virus in mosquitoes from Xinjiang during next-generation sequencing arboviral surveillance.

Transbound Emerg Dis 2021 Mar 15;68(2):467-476. Epub 2020 Aug 15.

Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, PR China.

A total of 548 mosquitoes were collected from different animal farms located near to highly populated cities in Xinjiang and were subjected to metagenomic next-generation sequencing (mNGS). The mNGS data demonstrated that 18,842 (XJ1 strain) and 1,077 (XJ2 strain) of Japanese encephalitis virus (JEV)-related reads were detected in XJ1 and XJ2 mosquito samples collected from Wushi and Wensu counties of Aksu area, which accounted for 0.032% and 0.006% of the total clean reads generated from XJ1 and XJ2 samples, respectively. The Bayesian molecular phylogenetic analysis suggested that XJ1 and XJ2 strains belonged to JEV genotype III and were clustered with JEV strains isolated in China. Notably, Bayesian molecular time line phylogeny revealed that XJ1 strain shared its MRCA with JEV GSS strain about 67 YA, suggesting that XJ1 strain likely originated from linages closely related to GSS strain and spread to Xinjiang later. Overall, these findings suggest that Xinjiang was probably not free from JEV, and thus, a further surveillance of JEV is required in Xinjiang.
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http://dx.doi.org/10.1111/tbed.13697DOI Listing
March 2021

Unfractionated heparin inhibits histone-mediated coagulation activation and thrombosis in mice.

Thromb Res 2020 09 5;193:122-129. Epub 2020 Jun 5.

Department of Critical Care Medicine, The First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang 110001, Liaoning Province, China. Electronic address:

Introduction: Histones play pivotal roles in the pathophysiology of sepsis. Different studies have reported that unfractionated heparin (UFH) can improve histone-mediated organ dysfunction. However, in such studies, UFH was usually pretreated or injected with histones concurrently, which was obviously inconsistent with clinical practice. Therefore, this study aimed to figure out whether UFH can inhibit histone-induced coagulation activation and thrombosis when histones have caused coagulation disorder already.

Methods: Male C57/BL6 mice of average weight ~22 g were randomly divided into three groups. The histone group was injected with histones 50 mg/kg through the tail vein. The histone + UFH group was injected with UFH (400 U/kg) through the tail vein 1 h or 6 h after the induction of histones. The control group was injected with equal volume of sterile saline. The lungs were harvested 3 h after UFH administration. In survival studies, mice were treated with UFH (800 U/kg, n = 10) or sterile saline (n = 10) intravenously after histones (75 mg/kg) injection and observed for 7 days.

Results: 1) UFH improved survival rate in mice injected with lethal doses of histones; 2) UFH alleviated histone-induced lung injury and pulmonary edema; 3) UFH improved histone-induced endothelial cell injury; 4) UFH improved histone-mediated high expression of TF, PAI-1, fibrinogen and low expression of TM.

Conclusion: UFH can effectively attenuate histone-induced lung injury, coagulation activation and thrombosis.
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http://dx.doi.org/10.1016/j.thromres.2020.06.007DOI Listing
September 2020

gp91, a Novel Biomarker Evaluating Oxidative Stress, Is Elevated in Subclinical Hypothyroidism.

Int J Endocrinol 2020 6;2020:3161730. Epub 2020 May 6.

Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021 Shandong, China.

Background: gp91, 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 gp91 were measured to assess the oxidative stress in patients with SH. And the relationship among gp91, 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 ( = 13), controls with high level of LDL-C alone ( = 12), SH with normal level of LDL-C ( = 11), and SH with high level of LDL-C ( = 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, < 0.001), controls with high level of LDL-C (61.21 ± 4.48 ug/mL, =0.038) and SH with a normal level of LDL-C (62.82 ± 11.67ug/mL, =0.027). Additionally, the levels of gp91 showed a significant positive correlation with both the levels of LDL-C ( = 0.595, < 0.001) and TSH ( = 0.346, =0.013) by the Spearman correlation analyses. The correlation remained significant even when the effect of another factor was controlled (TSH: when the effect of LDL-C was controlled,  = 0.453, =0.001; LDL-C: when the effect of TSH was controlled,  = 0.291, =0.040). The main effect analysis showed an independent main effect of either LDL-C ( = 0.041) or TSH (=0.022) on gp91 without interaction (=0.299).

Conclusions: Our work demonstrated that the levels of gp91, a novel biomarker for measuring the oxidative stress, were significantly elevated in the patients with SH. And LDL-C and TSH were both independent predictors of gp91. BMI : Body mass index; TC : Total cholesterol; LDL-C : Low-density lipoprotein cholesterol; HDL-C : High-density lipoprotein cholesterol; TG : Triglyceride; FBG : Fasting blood glucose; FT3 : Free triiodothyronine; FT4 : Free thyroxine; TSH: Thyroid stimulating hormone; SBP : Systolic blood pressure; DBP : Diastolic blood pressure; SD : Standard deviation; LSD: Least significant difference.
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http://dx.doi.org/10.1155/2020/3161730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225862PMC
May 2020
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