Publications by authors named "Huaqing Shu"

19 Publications

  • Page 1 of 1

Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury.

Hereditas 2021 Apr 16;158(1):13. Epub 2021 Apr 16.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277, Jiefang Avenue, Wuhan, 430022, China.

Background: Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI).

Methods: Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI.

Results: We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future.

Conclusions: Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.
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http://dx.doi.org/10.1186/s41065-021-00176-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052759PMC
April 2021

The peak levels of highly sensitive troponin I predicts in-hospital mortality in COVID-19 patients with cardiac injury: a retrospective study.

Eur Heart J Acute Cardiovasc Care 2021 Mar;10(1):6-15

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Ave, Wuhan, 430022 Hubei, China.

Aims: To investigate the association between levels of highly sensitive troponin I (hs-troponin I) and mortality in novel coronavirus disease 2019 (COVID-19) patients with cardiac injury.

Methods And Results: We retrospectively reviewed the medical records of all COVID-19 patients with increased levels of hs-troponin I from two hospitals in Wuhan, China. Demographic information, laboratory test results, cardiac ultrasonographic findings, and electrocardiograms were collected, and their predictive value on in-hospital mortality was explored using multivariable logistic regression. Of 1500 patients screened, 242 COVID-19 patients were enrolled in our study. Their median age was 68 years, and (48.8%) had underlying cardiovascular diseases. One hundred and seventy-six (72.7%) patients died during hospitalization. Multivariable logistic regression showed that C-reactive protein (>75.5 mg/L), D-dimer (>1.5 μg/mL), and acute respiratory distress syndrome were risk factors of mortality, and the peak hs-troponin I levels (>259.4 pg/mL) instead of the hs-troponin I levels at admission was predictor of death. The area under the receiver operating characteristic curve of the peak levels of hs-troponin I for predicting in-hospital mortality was 0.79 (95% confidence interval, 0.73-0.86; sensitivity, 0.80; specificity, 0.72; P < 0.0001).

Conclusion: Our results demonstrated that the risk of in-hospital death among COVID-19 patients with cardiac injury can be predicted by the peak levels of hs-troponin I during hospitalization and was significantly associated with oxygen supply-demand mismatch, inflammation, and coagulation.
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http://dx.doi.org/10.1093/ehjacc/zuaa019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665398PMC
March 2021

Extracorporeal Membrane Oxygenation for SARS-CoV-2 Acute Respiratory Distress Syndrome: A Retrospective Study From Hubei, China.

Front Med (Lausanne) 2020 12;7:611460. Epub 2021 Jan 12.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO/FiO of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.
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http://dx.doi.org/10.3389/fmed.2020.611460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835137PMC
January 2021

A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure.

Front Med (Lausanne) 2020 8;7:607821. Epub 2020 Dec 8.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

High-flow nasal cannula (HFNC) has been recommended as a suitable choice for the management of coronavirus disease 2019 (COVID-19) patients with acute hypoxemic respiratory failure before mechanical ventilation (MV); however, delaying MV with HFNC therapy is still a dilemma between the technique and clinical management during the ongoing pandemic. Retrospective analysis of COVID-19 patients treated with HFNC therapy from four hospitals of Wuhan, China. Demographic information and clinical variables before, at, and shortly after HFNC initiation were collected and analyzed. A risk-stratification model of HFNC failure (the need for MV) was developed with the 324 patients of Jin Yin-tan Hospital and validated its accuracy with 69 patients of other hospitals. Among the training cohort, the median duration of HFNC therapy was 6 (range, 3-11), and 147 experienced HFNC failure within 7 days of HFNC initiation. Early predictors of HFNC failure on the basis of a multivariate regression analysis included age older than 60 years [odds ratio (OR), 1.93; 95% confidence interval (CI), 1.08-3.44; = 0.027; 2 points], respiratory rate-oxygenation index (ROX) <5.31 (OR, 5.22; 95% CI, 2.96-9.20; < 0.001; 5 points) within the first 4 h of HFNC initiation, platelets < 125 × 10/L (OR, 3.04; 95% CI, 1.46-6.35; = 0.003; 3 points), and interleukin 6 (IL-6) >7.0 pg/mL (OR, 3.34; 95% CI, 1.79-6.23; < 0.001; 3 points) at HFNC initiation. A weighted risk-stratification model of these predictors showed sensitivity of 80.3%, specificity of 71.2% and a better predictive ability than ROX index alone [area under the curve (AUC) = 0.807 vs. 0.779, < 0.001]. Six points were used as a cutoff value for the risk of HFNC failure stratification. The HFNC success probability of patients in low-risk group (84.2%) was 9.84 times that in the high-risk group (34.8%). In the subsequent validation cohort, the AUC of the model was 0.815 (0.71-0.92). Aged patients with lower ROX index, thrombocytopenia, and elevated IL-6 values are at increased risk of HFNC failure. The risk-stratification models accurately predicted the HFNC failure and early stratified COVID-19 patients with HFNC therapy into relevant risk categories.
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http://dx.doi.org/10.3389/fmed.2020.607821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793962PMC
December 2020

Correction to: Dynamic Changes of Antibodies to SARS-CoV-2 in COVID-19 Patients at Early Stage of Outbreak.

Virol Sin 2020 Dec;35(6):887

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

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http://dx.doi.org/10.1007/s12250-020-00318-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683590PMC
December 2020

A 58-Year-Old Man in Respiratory Distress After Lung Lobectomy.

Chest 2020 09;158(3):e135-e137

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2019.09.044DOI Listing
September 2020

Incidence and Risk Factors of Deep Vein Thrombosis in Hospitalized COVID-19 Patients.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620953217

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Deep vein thrombosis (DVT) is prevalent in patients with coronavirus disease 2019 (COVID-19). However, the risk factors and incidence rate of DVT remains elusive. Here, we aimed to assess the incidence rate and risk factors of DVT. All patients diagnosed with COVID-19 and performed venous ultrasound by ultrasound deparment between December 2019 and April 2020 in Wuhan Jin Yin-tan hospital were enrolled. Demographic information and clinical features were retrospectively collected. Notably, a comparison between the DVT and the non-DVT groups was explored. The incidence rate of venous thrombosis was 35.2% (50 patients out of 142). Moreover, the location of thrombus at the proximal extremity veins was 5.6% (n = 8), while at distal extremity veins was 35.2% (n = 50) of the patients. We also noted that patients with DVT exhibited a high level of D-dimer (OR 10.9 (95% CI, 3.3-36.0), < 0.001), were admitted to the intensive care unit (OR 6.5 (95% CI, 2.1-20.3), = 0.001), a lower usage of the anticoagulant drugs (OR 3.0 (95% CI, 1.1-7.8), < 0.001). Finally, this study revealed that a high number of patients with COVID-19 developed DVT. This was observed particularly in critically ill patients with high D-dimer levels who required no anticoagulant medication.
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http://dx.doi.org/10.1177/1076029620953217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457409PMC
September 2020

HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs.

Cell Immunol 2020 10 7;356:104192. Epub 2020 Aug 7.

Department of Critical Care Medicine, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China. Electronic address:

Background: CD4CD25FoxP3 T helper cells (Tregs), a subgroup of CD4 T helper cells, are critical effectors that protect against acute lung injury (ALI) by contact-dependent suppression or releasing anti-inflammatory cytokines including interleukin-10 (IL-10), and transforming growth factor (TGF-β). HMGB1 (High mobility group box 1 protein) was identified as a nuclear non-histone DNA-binding chromosomal protein, which participates in the regulation of lung inflammatory response and pathological processes in ALI. Previous studies have suggested that Tregs overexpresses the HMGB1-recognizing receptor. However, the interaction of HMGB1 with Tregs in ALI is still unclear.

Objective: To investigate whether HMGB1 aggravates ALI by suppressing immunosuppressive function of Tregs.

Methods: Anti-HMGB1 antibody and recombinant mouse HMGB1 (rHMGB1) were administered in lipopolysaccharide (LPS)-induced ALI mice and polarized LPS-primed Tregs in vitro. The Tregs pre-stimulated with or without rHMGB1 were adoptively transferred to ALI mice and depleted by Diphtheria toxin (DT). For coculture experiment, isolated Tregs were first pre-stimulated with or without rHMGB1 or anti-HMGB1 antibody, then they were cocultured with bone marrow-derived macrophages (BMMs) under LPS stimulation.

Results: Tregs protected against acute lung pathological injury. HMGB1 modulated the suppressive function of Tregs as follows: reduction in the number of the cells and the activity of Tregs, the secretion of anti-inflammatory cytokines (IL-10, TGF-β) from Tregs, the production of IL-2 from CD4 T cells and CD11c DCs, and the M2 polarization of macrophages, as well as inducing proinflammatory response of macrophages.

Conclusions: HMGB1 could aggravate LPS induced-ALI through suppressing the activity and function of Tregs.
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http://dx.doi.org/10.1016/j.cellimm.2020.104192DOI Listing
October 2020

Dynamic Changes of Antibodies to SARS-CoV-2 in COVID-19 Patients at Early Stage of Outbreak.

Virol Sin 2020 Dec 27;35(6):744-751. Epub 2020 Jul 27.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has spread around the world with high mortality. To diagnose promptly and accurately is the vital step to effectively control its pandemic. Dynamic characteristics of SARS-CoV-2-specific antibodies which are important for diagnosis of infection have not been fully demonstrated. In this retrospective, single-center, observational study, we enrolled the initial 131 confirmed cases of COVID-19 at Jin-Yin-Tan Hospital who had at least one-time antibody tested during their hospitalization. The dynamic changes of IgM and IgG antibodies to SARS-CoV-2 nucleocapsid protein in 226 serum samples were detected by ELISA. The sensitivities of IgM and IgG ELISA detection were analyzed. Result showed that the sensitivity of the IgG ELISA detection (92.5%) was significantly higher than that of the IgM (70.8%) (P < 0.001). The meantimes of seroconversion for IgM and IgG were 6 days and 3 days, respectively. The IgM and IgG antibody levels peaked at around 18 days and 23 days, and then IgM fell to below the baseline level at about day 36, whereas IgG maintained at a relatively high level. In conclusion, antibodies should be detected to aid in diagnosis of COVID-19 infection. IgG could be a sensitive indicator for retrospective diagnosis and contact tracing, while IgM could be an indicator of early infection.
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http://dx.doi.org/10.1007/s12250-020-00268-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383121PMC
December 2020

Corrigendum to Resolvin D1 Attenuates Lipopolysaccharide Induced Acute Lung Injury Through CXCL-12/CXCR4 Pathway [J Surg Res. 2014 May 1;188(1):213-221].

J Surg Res 2020 08;252:285

Department of Anesthesiology and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1016/j.jss.2020.03.049DOI Listing
August 2020

High-fluorescent lymphocytes are increased in patients with COVID-19.

Br J Haematol 2020 07 8;190(2):e76-e78. Epub 2020 Jun 8.

Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1111/bjh.16867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276851PMC
July 2020

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.

Lancet Respir Med 2020 05 24;8(5):475-481. Epub 2020 Feb 24.

Department of Critical Care Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Anesthesiology and Critical Care Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Jin Yin-tan Hospital, Wuhan, China. Electronic address:

Background: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia.

Methods: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation.

Findings: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients.

Interpretation: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced.

Funding: None.
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http://dx.doi.org/10.1016/S2213-2600(20)30079-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102538PMC
May 2020

Detection of an inferior vena cava thrombus in transit by ultrasound.

Intensive Care Med 2020 01 18;46(1):126-127. Epub 2019 Sep 18.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1007/s00134-019-05779-8DOI Listing
January 2020

Hyperforin Promotes Post-stroke Neuroangiogenesis via Astrocytic IL-6-Mediated Negative Immune Regulation in the Ischemic Brain.

Front Cell Neurosci 2019 7;13:201. Epub 2019 May 7.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hyperforin has been shown to be capable of promoting angiogenesis and functional recovery after ischemic stroke in our previous study. However, the exact mechanisms involved are not fully elucidated. In this study, adult male mice were subjected to 60-min transient middle cerebral artery occlusion followed by reperfusion for 28 days. Hyperforin was administrated to MCAO mice every 24 h for 2 weeks starting at 14 days post-ischemia (dpi). Then flow cytometry, quantitative Real-time PCR (RT-qPCR), western blotting, immunohistochemistry, and functional assays were performed to explore the molecular mechanisms and . Our data showed that hyperforin increased astrocytic interleukin (IL)-6 in the ischemic hemisphere via TLR4 at 28 dpi. The astrocytic IL-6 was essential to the promoting effects of hyperforin on the neural precursor cells proliferation, neuronal differentiation, angiogenesis, and functional recovery after stroke. Furthermore, hyperforin promoted the infiltration of regulatory T cells (Tregs) to the ischemic hemisphere and increased Tregs-derived cytokine IL-10 and transforming growth factor-β (TGF-β) in a manner that was dependent on astrocytic IL-6. Astrocytic IL-6 was critical to the role of hyperforin in promoting the infiltration of T-helper (Th) type 2 cells to the ischemic hemisphere and Th2-derived cytokine IL-4, relative to Th1 and Th1-derived cytokine interferon-γ (IFN-γ), which decreased during stroke recovery. After depletion of CD25 Tregs, the promoting effects of hyperforin on post-stroke neurogenesis was attenuated. Moreover, blockade of IL-4 and TGF-β abrogated the promoting role of hyperforin in post-stroke neurogenesis, angiogenesis and functional recovery. Our results reveal a previously uncharacterized role of astrocytic IL-6-mediated negative immune regulation in the promoting effects of hyperforin on post-stroke neurovascular regeneration and functional recovery.
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http://dx.doi.org/10.3389/fncel.2019.00201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514137PMC
May 2019

BML-111 Reduces Neuroinflammation and Cognitive Impairment in Mice With Sepsis via the SIRT1/NF-κB Signaling Pathway.

Front Cell Neurosci 2018 21;12:267. Epub 2018 Aug 21.

Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Sepsis is a life-threatening state of organ dysfunction caused by infection and which can induce severe neurological disorders that lead to neuroinflammation and cognitive impairment. Inflammation has been reported to cause neuronal apoptosis in sepsis, which can finally lead to cognitive impairment. Previous studies have suggested that BML-111 can exhibit anti-inflammatory and proresolution activities. Additionally, silent information regulator 1 (SIRT1) can inhibit the NF-κB signaling pathway in an inflammation state. However, the role of the SIRT1/NF-κB signaling pathway in the protective effects of BML-111 against sepsis-induced neuroinflammation and cognitive impairment remains unclear. This study aimed to determine the effects of BML-111 on neuroinflammation and cognitive impairment induced by sepsis. Male C57BL/6J mice were subjected to cecal ligation and puncture (CLP) or a sham operation. BML-111 was administered via intracerebroventricular injection (0.1 mg/kg) immediately after CLP. Boc-2 (50 μg/kg) was administered intracerebroventricularly 30 min before CLP, and EX527 (10 μg) was administered every 2 days for a total of three times before CLP, also intracerebroventricularly. Some of the surviving mice underwent open-field, novel-object-recognition, and fear-conditioning behavioral tests at 7 days after surgery. Some of the other surviving mice were killed at 24 h after surgery to assess synaptic damage (PSD95 and Synapsin1), markers of inflammation [tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β], cytoplasmic p65, nuclear p65, Ac- NF-κB and SIRT1. At 48 h after CLP, TUNEL and glia-activation by immunofluorescence investigations were performed on a separate cohort of surviving animals. The results suggested that sepsis resulted in cognitive impairment, which was accompanied by the decreased the expression of PSD95 and Synapsin1, increased amount of TUNEL-positive cells and the activation of glias, increased production of TNF-α and IL-1β, increased expression of nuclear p65, Ac- NF-κB, and decreased expression of SIRT1 and cytoplasmic p65. It is especially notable that these abnormalities could be reduced by BML-111 treatment. EX527, an SIRT1 inhibitor, abolished the effects of BML-111. These results demonstrate that BML-111 can reduce the neuroinflammation and cognitive impairment induced by sepsis via SIRT/NF-κB signaling pathway.
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http://dx.doi.org/10.3389/fncel.2018.00267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110933PMC
August 2018

Argon preconditioning enhances postischaemic cardiac functional recovery following cardioplegic arrest and global cold ischaemia.

Eur J Cardiothorac Surg 2018 09;54(3):539-546

Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.

Objectives: Previous studies demonstrated that preconditioning with argon gas provided a marked reduction in inflammation and apoptosis and increased myocardial contractility in the setting of acute myocardial ischaemia-reperfusion (IR). There is substantial evidence that myocardial IR injury following cardioplegic arrest is associated with the enhancement of apoptosis and inflammation, which is considered to play a role in cardiac functional impairment. Therefore, the present study was designed to clarify whether preconditioning with argon gas enhances recovery of cardiac function following cardioplegic arrest.

Methods: Sprague-Dawley rats were anaesthetized and ventilated and allocated to (i) the control group (control IR, n = 10) and (ii) the in vivo group (argon IR), which received 3 cycles of argon (50% argon, 21% oxygen and 29% nitrogen, n = 10) administered for 5 min interspersed with 5 min of a gas mixture (79% nitrogen and 21% oxygen). The hearts were excised and then evaluated in an erythrocyte-perfused isolated working heart system. Cold ischaemia (4°C) for 60 min was induced by histidine-tryptophan-ketoglutarate cardioplegia, followed by 40 min of reperfusion. Cardiac functional parameters were assessed. In left ventricular tissue samples, the expressions of extracellular-regulated kinase (ERK1/2), AKT serine/threonine kinase (Akt), jun N-terminal kinase (JNK), endothelial nitric oxide synthase (eNOS) and HMGB1: high-mobility group box 1 (HMGB1) protein were assessed by western blot, and high-energy phosphates were evaluated by high-performance liquid chromatography.

Results: At the end of reperfusion, the rats preconditioned with argon showed significantly enhanced recovery of cardiac output (101 ± 6% vs 87 ± 11%; P < 0.01), stroke volume (94 ± 4% vs 80 ± 11%; P = 0.001), external heart work (100 ± 6% vs 81 ± 13%; P < 0.001) and coronary flow (90 ± 13% vs 125 ± 21%; P < 0.01) compared with the control IR group. These results were accompanied by a significant increase in the levels of myocardial phosphocreatine (23.71 ± 2.07 µmol/g protein vs the control IR group, 13.50 ± 4.75; P = 0.001) and maintained adenosine triphosphate levels (13.62 ±1.89 µmol/g protein vs control IR group adenosine triphosphate: 10.08 ± 1.94 µmol/g; P = 0.017). Additionally, preconditioning with argon markedly reduced the activation of JNK (0.11 ± 0.01 vs 0.25 ± 0.03; P = 0.005) and the expression of HMGB1 protein (0.52 ± 0.04 vs 1.5 ± 0.10; P < 0.001) following reperfusion.

Conclusions: Preconditioning with argon enhanced cardiac functional recovery in rat hearts arrested with histidine-tryptophan-ketoglutarate cardioplegia, thereby representing a potential novel cardioprotective approach in cardiac surgery.
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http://dx.doi.org/10.1093/ejcts/ezy104DOI Listing
September 2018

Restrictive Fluid Resuscitation Leads to Better Oxygenation than Non-Restrictive Fluid Resuscitation in Piglets with Pulmonary or Extrapulmonary Acute Respiratory Distress Syndrome.

Med Sci Monit 2015 Jul 12;21:2008-20. Epub 2015 Jul 12.

Department of Anesthesiology and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).

Background: Early goal-directed therapy (EGDT) is used to reduce mortality from septic shock and could be used in early fluid resuscitation of acute respiratory distress syndrome (ARDS). The aim of the present study was to assess the effects of restrictive (RFR) and nonrestrictive fluid resuscitation (NRFR) on hemodynamics, oxygenation, pulmonary function, tissue perfusion, and inflammation in piglets with pulmonary or extrapulmonary ARDS (ARDSp and ARDSexp).

Material And Methods: Chinese miniature piglets (6-8 weeks; 15 ± 1 kg) were randomly divided into 2 groups (n=12/group) for establishing ARDSp and ARDSexp models, and were further divided into 2 subgroups (n=6/subgroup) for performing RFR and NRFR. Piglets were anesthetized and hemodynamic, pulmonary, and oxygenation indicators were collected at different time points for 6 hours. The goal of EGDT was set for PiCCO parameters (mean arterial pressure (MAP), urine output and cardiac index (CI), and central venous oxygen saturation (ScvO2).

Results: Piglets under RFR had lower urine output compared with NRFR, as well as lower total fluid volume (P<0.05). EVLW was decreased in ARDSp+RFR and NRFR, as well as in ARDSexp+RFR, but EVLW increased in ARDSexp+NRFR (P<0.05). PaO2/FiO2 decreased in ARDSp using both methods, but was higher with RFR (P<0.05), and was increased in ARDSexp+RFR. Other pulmonary indicators were comparable. The anti-inflammatory cytokines IL-10 and LXA4 were increased in ARDSexp after RFR (P<0.05), but not in the other groups.

Conclusions: RFR led to better oxygenation in ARDSp and ARDSexp compared with NRFR, but fluid restriction improved oxygenation in ARDSexp only.
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http://dx.doi.org/10.12659/MSM.892734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514267PMC
July 2015

Resolvin D1 attenuates lipopolysaccharide induced acute lung injury through CXCL-12/CXCR4 pathway.

J Surg Res 2014 May 6;188(1):213-21. Epub 2013 Dec 6.

Department of Anesthesiology and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: The recruitment of neutrophils plays an important role in the progress of acute lung injury (ALI). Excessive neutrophils released from bone marrow accumulate in lung, release proinflammatory factors, and cause tissue damage. CXCL-12/CXCR4 is an important signaling pathway, which regulates the migration of bone marrow hematopoietic cells out of bone marrow and involves in neutrophil accumulation and retention in the inflammatory site. Resolvin D1 (RvD1) is a kind of lipid mediators, which can alleviate many inflammatory diseases. We hypothesized that RvD1 can alleviate lipopolysaccharide (LPS)-induced ALI through regulating CXCL-12/CXCR4 pathway.

Methods: We randomized mice into five groups: control group, RvD1 group, LPS group, LPS plus RvD1 group, and LPS plus AMD3100 group. ALI was established by intratracheal instillation of LPS. After 24 and 72 h, mice were sacrificed, and lung tissues were harvested for histologic analysis, wet-to-dry ratio, myeloperoxidase activity, and CXCL-12 expression. Bronchoalveolar fluid was collected for protein analysis, cytokines assay, and flow cytometry analysis.

Results: Histologic findings as well as wet-to-dry ratio, protein concentration, cytokines assay, neutrophil number, and myeloperoxidase activity confirmed that RvD1 and AMD3100 alleviated LPS-induced ALI. RvD1 decreased CXCL-12 messenger RNA expression in lung. However, RvD1 promoted CXCR4 expression in neutrophils in the initial stage of inflammation and reduced its level in the later stage.

Conclusions: RvD1 protects LPS-induced ALI partially through regulating CXCL-12/CXCR4 pathway.
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http://dx.doi.org/10.1016/j.jss.2013.11.1107DOI Listing
May 2014

Mechanical stretch induces pentraxin 3 release by alveolar epithelial cells in vitro.

Med Sci Monit 2009 May;15(5):BR135-40

Department of Anesthesiology, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology,Wuhan, Hubei Province, China.

Background: Inflammation and pulmonary injury caused by mechanical ventilation is a complex process in which long pentraxin 3 (PTX3) is suggested to play an important role. The effect of mechanical stretch on PTX3 mRNA and protein expression in human alveolar epithelial cells (A549) was investigated.

Material/methods: Immortalized A549 cells were exposed to tightly controlled and physiologically relevant cyclic mechanical stretch. A549 cells grown on collagen I BioFlex plates were exposed to square cyclic stretch at 0.3 Hz using the Flexercell system with 6% or 20% elongation of cells. In another group, cells were pretreated with small interfering RNA directed against PTX3 before stretch. After stretching, conditioned media and cells were collected and analyzed by Western blotting. Real-time PCR of cDNA generated from the stretched cells was performed. Apoptosis and viability of the cells following treatment were assessed using standard procedures.

Results: Mechanical cyclic stretch of 20% elongation led to increased PTX3 gene expression, increased release of PTX3 protein, and induced apoptosis and necrosis in A549 cells. Expression of PTX3 highly correlated with the severity of apoptosis. However, the results suggest that PTX3 expression was significantly reduced by pretreatment of the A549 cells with small interfering RNA of PTX3.

Conclusions: PTX3 may be an important mediator of lung tissue damage associated with mechanical stretch. Determining the production and regulation of PTX3 during mechanical ventilation may be critical in preventing or reducing ventilator-induced lung injury.
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May 2009