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Polyethylene terephthalate (PET) is a polymer synthesized via the dehydration and condensation reaction between ethylene glycol and terephthalic acid. PET has emerged as one of the most extensively employed plastic materials due to its exceptional plasticity and durability. Nevertheless, PET has a complex structure and is extremely difficult to degrade in nature, causing severe pollution to the global ecological environment and posing a threat to human health. Currently, the methods for PET processing mainly include physical, chemical, and biological methods. Biological enzyme degradation is considered the most promising PET degradation method. In recent years, an increasing number of enzymes that can degrade PET have been identified, and they primarily target the ester bond of PET. This review comprehensively introduced the latest research progress in PET enzymatic degradation from the aspects of PET-degrading enzymes, PET biodegradation pathways, the catalytic mechanism of PET-degrading enzymes, and biotechnological strategies for enhancing PET-degrading enzymes. On this basis, the current challenges within the enzymatic PET degradation process were summarized, and the directions that need to be worked on in the future were pointed out. This review provides a reference and basis for the subsequent effective research on PET biodegradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) trial demonstrated that intensive systolic blood pressure (SBP) lowering has cardiovascular benefits. However, the influence of baseline diastolic blood pressure (DBP) on the effects of intensive blood pressure lowering on cardiovascular outcomes has not been fully elucidated., Methods: We performed a post hoc analysis of the STEP trial. Participants were randomly allocated to intensive (110 to <130 mm Hg) or standard (130 to <150 mm Hg) treatment groups. The effects of intensive SBP lowering on the primary composite outcome (stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, and cardiovascular death), major adverse cardiac event (a composite of the individual components of the primary outcome except for stroke), and all-cause mortality were analyzed according to baseline DBP as both a categorical and a continuous variable., Results: The 8259 participants had a mean age of 66.2±4.8 years, and 46.5% were men. Participants with lower DBP were slightly older and had greater histories of cardiovascular disease, diabetes, and hyperlipidemia. Within each baseline DBP quartile, the mean achieved DBP was lower in the intensive versus standard group. The effects of intensive SBP lowering were not modified by baseline DBP as a continuous variable or as a categorical variable (quartiles, or <70, 70 to <80, and ≥80 mm Hg; all P value for interaction >0.05)., Conclusions: The beneficial effects of intensive SBP lowering on cardiovascular outcomes were unaffected by baseline DBP. Lower DBP should not be an obstacle to intensive SBP control., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311., Competing Interests: Disclosures None.

Plastics are widely used in human daily life, which bring great convenience. Nevertheless, the disposal of a large amount of plastic wastes also brings great pressure to the environment. Polyethylene terephthalate (PET) is a polymer thermoplastic material produced from petroleum. It has become one of the most commonly used plastics in the world due to its durability, high transparency, light weight and other characteristics. PET can exist in nature for a long time due to its complex structure and the difficulty in degradation, which causes serious pollution to the global ecological environment, and threatens human health. The degradation of PET wastes has since become one of the global challenges. Compared with physical and chemical methods, biodegradation is the greenest way for treating PET wastes. This review summarizes the recent advances on PET biodegradation including microbial and enzymatic degradation of PET, biodegradation pathway, biodegradation mechanisms, and molecular modification of PET-degrading enzymes. In addition, the prospect for achieveing efficient degradation of PET, searching and improving microorganisms or enzymes that can degrade PET of high crystallinity are presented, with the aimto facilitate the development, application and molecular modification of PET biodegradation microorganisms or enzymes.

Myocardial infarction that causes damage to heart muscle can lead to heart failure. The identification of molecular mechanisms promoting myocardial regeneration represents a promising strategy to improve cardiac function. Here we show that IGF2BP3 plays an important role in regulating adult cardiomyocyte proliferation and regeneration in a mouse model of myocardial infarction. IGF2BP3 expression progressively decreases during postnatal development and becomes undetectable in the adult heart. However, it becomes upregulated after cardiac injury. Both gain- and loss-of-function analyses indicate that IGF2BP3 regulates cardiomyocyte proliferation in vitro and in vivo. In particular, IGF2BP3 promotes cardiac regeneration and improves cardiac function after myocardial infarction. Mechanistically, we demonstrate that IGF2BP3 binds to and stabilizes MMP3 mRNA through interaction with N 6 -methyladenosine modification. The expression of MMP3 protein is also progressively downregulated during postnatal development. Functional analyses indicate that MMP3 acts downstream of IGF2BP3 to regulate cardiomyocyte proliferation. These results suggest that IGF2BP3-mediated post-transcriptional regulation of extracellular matrix and tissue remodeling contributes to cardiomyocyte regeneration. They should help to define therapeutic strategy for ameliorating myocardial infarction by inducing cell proliferation and heart repair., (© 2023. The Author(s).)

Background: Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms., Methods: Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay., Results: In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes., Conclusions: Our study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis., (© 2023. The Author(s).)

N6-methyladenosine (m6A) modification accounts for the most prevalent mRNA internal modification and has emerged as a widespread regulatory mechanism in multiple physiological processes. We address a role of methyltransferase-like protein 3 (METTL3) in neutrophil activation. METTL3 controls neutrophil release from bone marrow to circulation through surface expression of CXC chemokine receptor 2 (CXCR2) in a Toll-like receptor 4 (TLR4) signaling-dependent manner in lipopolysaccharide (LPS)-induced endotoxemia. We show that the mRNA of TLR4 is modified by m6A, exhibiting increased translation and slowed degradation simultaneously, leading to elevated protein levels of TLR4, which eventually promotes the TLR4 signaling activation of neutrophil. The reduced expression of TLR4 lowers cytokine secretion in METTL3-deleted neutrophils upon LPS stimulation through TLR4/Myd88/nuclear factor κB (NF-κB) signaling. Collectively, these data demonstrate that METTL3 modulation of TLR4 expression is a critical determinant of neutrophil activation in endotoxemia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Sepsis-induced apoptosis leads to lymphopenia including the decrease of CD4 + T cells thus favoring immunosuppression., Objectives: Although epidermal growth factor receptor (EGFR) inhibitors significantly improve the survival rate of septic mice, the effect of EGFR on the function and metabolism of CD4 + T cells in sepsis remained unknown., Methods: CD4 + T cells from septic mice and patients were assessed for apoptosis, activation, Warburg metabolism and glucose transporter 1 (Glut1) expression with or without the interference of EGFR activation., Results: EGFR facilitates CD4 + T cell activation and apoptosis through Glut1, which is a key enzyme that controls glycolysis in T cells. EGFR, TANK binding kinase 1 (TBK1) and Glut1 form a complex to facilitate Glut1 transportation from cytoplasm to cell surface. Both the levels of membrane expression of EGFR and Glut1 and the activation levels of CD4 + T cells were significantly higher in patients with sepsis as compared with healthy subjects., Conclusion: Our data demonstrated that through its downstream TBK1/Exo84/RalA protein system, EGFR regulates Glut1 transporting to the cell surface, which is a key step for inducing the Warburg effect and the subsequent cellular activation and apoptosis of CD4 + T lymphocytes and may eventually affect the immune functional status, causing immune cell exhaustion in sepsis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Production and hosting by Elsevier B.V.)

EGFR phosphorylation is required for TLR4-mediated macrophage activation during sepsis. However, whether and how intracellular EGFR is transported during endotoxemia have largely been unknown. Here, we show that LPS promotes high levels cell surface expression of EGFR in macrophages through two different transport mechanisms. On one hand, Rab10 is required for EEA1-mediated the membrane translocation of EGFR from the Golgi. On the other hand, EGFR phosphorylation prevents its endocytosis in a kinase activity-dependent manner. Erlotinib, an EGFR tyrosine kinase inhibitor, significantly reduced membrane EGFR expression in LPS-activated macrophage. Mechanistically, upon LPS induced TLR4/EGFR phosphorylation, MAPK14 phosphorylated Rab7a at S72 impaired membrane receptor late endocytosis, which maintains EGFR membrane localization though blocking its lysosomal degradation. Meanwhile, Rab5a is also involved in the early endocytosis of EGFR. Subsequently, inhibition of EGFR phosphorylation switches M1 phenotype to M2 phenotype and alleviates sepsis-induced acute lung injury. Mechanistic study demonstrated that Erlotinib suppressed glycolysis-dependent M1 polarization via PKM2/HIF-1ɑ pathway and promoted M2 polarization through up-regulating PPARγ induced glutamine metabolism. Collectively, our data elucidated a more in-depth mechanism of macrophages activation, and provided stronger evidence supporting EGFR as a potential therapeutic target for the treatment of sepsis., (© 2022. The Author(s).)

Long non-coding RNAs (lncRNAs) were reported to potentially play a regulatory role in the process of myocardial regeneration in the neonatal mouse. N6-methyladenosine (m 6 A) modification may play a key role in myocardial regeneration in mice and regulates a variety of biological processes through affecting the stability of lncRNAs. However, the map of m 6 A modification of lncRNAs in mouse cardiac development still remains unknown. We aimed to investigate the differences in the m 6 A status of lncRNAs during mouse cardiac development and reveal a potential role of m 6 A modification modulating lncRNAs in cardiac development and myocardial regeneration during cardiac development in mice. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) of the heart tissue in C57BL/6 J mice at postnatal day 1 (P1), P7 and P28 were performed to produce stagewise cardiac lncRNA m 6 A-methylomes in a parallel timeframe with the established loss of an intrinsic cardiac regeneration capacity and early postnatal development. There were significant differences in the distribution and abundance of m 6 A modifications in lncRNAs in the P7 vs P1 mice. In addition, the functional role of m 6 A in regulating lncRNA levels was established for selected transcripts with METTL3 silencing in neonatal cardiomyocytes in vitro. Based on our MeRIP-qPCR experiment data, both lncGm15328 and lncRNA Zfp597, that were not previously associated with cardiac regeneration, were found to be the most differently methylated at P1-P7. These two lncRNAs sponged several miRNAs which further regulated multiple mRNAs, including some of which have previously been linked with cardiac regeneration ability. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that differential m 6 A modifications were more enriched in functions and cellular signalling pathways related to cardiomyocyte proliferation. Our data suggested that the m 6 A modification on lncRNAs may play an important role in the regeneration of myocardium and cardiac development., (© 2022. The Author(s).)

Background: Central venous catheter (CVC) insertion complications are a prevalent and important problem in the intensive care unit (ICU), and source control by immediate catheter removal is considered urgent in patients with septic shock suspected to be caused by catheter-related bloodstream infection (CRBSI). We sought to determine the impact of immediate reinsertion of a new catheter (IRINC) on mortality among patients after CVC removal for suspected CRBSI., Methods: A propensity score-matched cohort of patients with suspected CRBSI who underwent IRINC or no IRINC in a 32-bed ICU in a university hospital in China from January 2009 through April 2021. Catheter tip culture and clinical symptoms were used to identify patients with suspected CRBSI. The Kaplan-Meier method was used to analyse 30-day mortality before and after propensity score matching, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality in the matched cohort were estimated with Cox proportional hazards models., Results: In total, 1,238 patients who had a CVC removed due to suspected CRBSI were identified. Among these patients, 877 (70.8%) underwent IRINC, and 361 (29.2%) did not. Among 682 propensity score-matched patients, IRINC was associated with an increased risk of 30-day mortality (HR, 1.481; 95% CI, 1.028 to 2.134) after multivariable, multilevel adjustment. Kaplan-Meier analysis found that IRINC was associated with the risk of mortality both before matching (P = 0.00096) and after matching (P = 0.018). A competing risk analysis confirmed the results of the propensity score-matched analysis. The attributable risk associated with bloodstream infection was not significantly different (HR, 1.081; 95% CI 0.964 to 1.213) among patients with suspected CRBSI in terms of 30-day mortality compared with that associated with other infections., Conclusions: In this cohort study, IRINC was associated with higher 30-day mortality compared to delayed CVC or no CVC among patients with suspected CRBSI. A large-sample randomized controlled trial is needed to define the best management for CVC in cases of suspected CRBSI because IRINC may also be associated with noninfectious complications. Trial registration This study was registered with the China Clinical Trials Registry (URL: http://www.chictr.org.cn/index.aspx ) under the following registration number: ChiCTR1900022175., (© 2022. The Author(s).)

The global coronavirus disease 2019 (COVID-19) pandemic has led to a health crisis. It remains unclear how anxiety affects blood pressure (BP) and cardiovascular risk among older patients with hypertension. In this study, we extracted longitudinal data on home BP monitored via a smartphone-based application in 3724 elderly patients with hypertension from a clinical trial (60-80 years; 240 in Wuhan and 3484 in non-Wuhan areas) to examine changes in morning BP during the COVID-19 outbreak in China. Anxiety was evaluated using Generalized Anxiety Disorder-7 item scores. Changes in morning systolic BP (SBP) were analyzed for five 30-day periods during the pandemic (October 21, 2019 to March 21, 2020), including the pre-epidemic, incubation, developing, outbreak, and plateau periods. Data on cardiovascular events were prospectively collected for one year. A total of 262 individuals (7.0%) reported an increased level of anxiety, and 3462 individuals (93.0%) did not. Patients with anxiety showed higher morning SBP than patients without anxiety, and the between-group differences in SBP change were +1.2 mmHg and +1.7 mmHg during the outbreak and plateau periods (P < 0.05), respectively. The seasonal BP variation in winter among patients with anxiety was suppressed during the pandemic. Anxious patients had higher rates of uncontrolled BP. During the 1-year follow-up period, patients with anxiety had an increased risk of cardiovascular events with a hazard ratio of 2.47 (95% confidence interval, 1.10-5.58; P = 0.03). In summary, COVID-19-related anxiety was associated with a short-term increase in morning SBP among older patients and led to a greater risk of cardiovascular events. (ClinicalTrials. gov number, NCT03015311)., (© 2022. The Author(s).)

Coronavirus disease-2019 (COVID-19) has rapidly spread worldwide and causes high mortality of elderly patients. High-flow nasal cannula therapy (HFNC) is an oxygen delivery method for severely ill patients. We retrospectively analyzed the course of illness and outcomes in 110 elderly COVID-19 patients (≥65 years) treated with HFNC from 6 hospitals. 38 patients received HFNC (200 mmHg < PaO 2 /FiO 2 ≤ 300 mmHg, early HFNC group), and 72 patients received HFNC (100 mmHg < PaO 2 /FiO 2 ≤ 200 mmHg, late HFNC group). There were no significant differences of sequential organ failure assessment (SOFA) scores and APECH II scores between early and late HFNC group on admission. Compared with the late HFNC group, patients in the early HFNC group had a lower likelihood of developing severe acute respiratory distress syndrome (ARDS), longer time from illness onset to severe ARDS and shorter duration of viral shedding after illness onset, as well as shorter lengths of ICU and hospital stay. 24 patients died during hospitalization, of whom 22 deaths (30.6%) were in the late HFNC group and 2 (5.3%) in the early HFNC group. The present study suggested that the outcomes were better in severely ill elderly patients with COVID-19 receiving early compared to late HFNC.

Introduction: Catheter management strategies for suspected catheter-related bloodstream infection (CRBSI) remain a major challenge in intensive care units (ICUs). The objective of this study was to determine the incidence, risk factors, and mortality attributable to CRBSIs in those patients., Methods: A population-based surveillance on suspected CRBSI was conducted from 2009 to 2018 in a tertiary care hospital in China. We used the results of catheter tip culture to identify patients with suspected CRBSIs. Demographics, systemic inflammatory response syndrome (SIRS) criteria, interventions, and microorganism culture results were analysed and compared between patients with and without confirmed CRBSIs. Univariate and multivariate analyses identified the risk factors for CRBSIs, and attributable mortality was evaluated with a time-varying Cox proportional hazard model., Results: In total, 686 patients with 795 episodes of suspected CRBSIs were included; 19.2% (153/795) episodes were confirmed as CRBSIs, and 17.4% (119/686) patients died within 30 days. The multifactor model shows that CRBSIs were associated with fever, hypotension, acute respiratory distress syndrome, hyperglycaemia and the use of continuous renal replacement therapy. The AUC was 77.0% (95% CI 73.3%-80.7%). The population attributable mortality fraction of CRBSI in patients was 18.2%, and mortality rate did not differ significantly between patients with and without CRBSIs (95% CI 0.464-1.279, P = 0.312)., Conclusions: This initial model based on the SIRS criteria is relatively better at identifying patients with CRBSI but only in domains of the sensitivity. There were no significant differences in attributable mortality due to CRBSI and other causes in patients with suspected CRBSI, which prompt catheter removal and re-insertion of new catheter may not benefit patients with suspected CRBSIs., Trial Registration: China Clinical Trials Registration number; ChiCTR1900022175.

Intracellular ion channel inositol 1,4,5-triphosphate receptor (IP3R1) releases Ca 2+ from endoplasmic reticulum. The disturbance of IP3R1 is related to several neurodegenerative diseases. This study investigated the mechanism of IP3R1 in myocardial ischemia/reperfusion (MI/R). After MI/R modeling, IP3R1 expression was silenced in myocardium of MI/R rats to explore its role in the concentration of myocardial enzymes, infarct area, Ca 2+ level, NLRP3/Caspase-1, and pyroptosis markers and inflammatory factors. The adult rat cardiomyocytes were isolated and cultured to establish hypoxia/reperfusion (H/R) cell model. The expression of IP3R1 was downregulated or ERP44 was overexpressed in H/R-induced cells. Nifedipine D6 was added to H/R-induced cells to block Ca 2+ channel or Nigericin was added to activate NLRP3. IP3R1 was highly expressed in myocardium of MI/R rats, and silencing IP3R1 alleviated MI/R injury, reduced Ca 2+ overload, inflammation and pyroptosis in MI/R rats, and H/R-induced cells. The binding of ERP44 to IP3R1 inhibited Ca 2+ overload, alleviated cardiomyocyte inflammation, and pyroptosis. The increase of intracellular Ca 2+ level caused H/R-induced cardiomyocyte pyroptosis through the NLRP3/Caspase-1 pathway. Activation of NLRP3 pathway reversed the protection of IP3R1 inhibition/ERP44 overexpression/Nifedipine D6 on H/R-induced cells. Overall, ERP44 binding to IP3R1 inhibits Ca 2+ overload, thus alleviating pyroptosis and MI/R injury.

The prevalence of cardiomyopathy is higher in diabetic patients than those without diabetes. Diabetic cardiomyopathy (DCM) is defined as a clinical condition of abnormal myocardial structure and performance in diabetic patients without other cardiac risk factors, such as coronary artery disease, hypertension, and significant valvular disease. Multiple molecular events contribute to the development of DCM, which include the alterations in energy metabolism (fatty acid, glucose, ketone and branched chain amino acids) and the abnormalities of subcellular components in the heart, such as impaired insulin signaling, increased oxidative stress, calcium mishandling and inflammation. There are no specific drugs in treating DCM despite of decades of basic and clinical investigations. This is, in part, due to the lack of our understanding as to how heart failure initiates and develops, especially in diabetic patients without an underlying ischemic cause. Some of the traditional anti-diabetic or lipid-lowering agents aimed at shifting the balance of cardiac metabolism from utilizing fat to glucose have been shown inadequately targeting multiple aspects of the conditions. Peroxisome proliferator-activated receptor α (PPARα), a transcription factor, plays an important role in mediating DCM-related molecular events. Pharmacological targeting of PPARα activation has been demonstrated to be one of the important strategies for patients with diabetes, metabolic syndrome, and atherosclerotic cardiovascular diseases. The aim of this review is to provide a contemporary view of PPARα in association with the underlying pathophysiological changes in DCM. We discuss the PPARα-related drugs in clinical applications and facts related to the drugs that may be considered as risky (such as fenofibrate, bezafibrate, clofibrate) or safe (pemafibrate, metformin and glucagon-like peptide 1-receptor agonists) or having the potential (sodium-glucose co-transporter 2 inhibitor) in treating DCM.

Certain miRNAs can attenuate hypoxia/re-oxygenation-induced autophagic cell death reported in our previous studies, but how these miRNAs regulate the autophagy-related cellular signaling pathway in preventing cell death is largely unknown. In the current study, the autophagy-related miRNAs of hsa-miR-20b were investigated in an in vitro model of hypoxia/re-oxygenation-induced endothelial autophagic cell death. Of these, miR-20b was found to be the most important miRNA which targeted on the key autophagy kinase ULK1 and inhibited hypoxia/re-oxygenation injury-induced autophagy by decreasing both autophagosomes and LC3I to II transition rate and P62 degradation. These processes were reversed by the transfection of an miR-20b inhibitor. Re-expression of ULK1 restores miR-20b-inhibited autophagy. Propofol, a commonly used anesthetic, promoted miR-20b and METTL3 expression and attenuated endothelial autophagic cell death. The inhibited endogenous expression of miR-20b or silenced METTL3 diminished the protective effect of propofol and accentuated autophagy. Additionally, METTL3 knockdown significantly inhibited miR-20b expression but up-regulated pri-miR-20b expression. Together, our data shows that propofol protects against endothelial autophagic cell death induced by hypoxia/re-oxygenation injury, associated with activation of METTL3/miR-20b/ULK1 cellular signaling.

Background: To investigate the effect of intravenous injection of dexmedetomidine combined with parecoxib sodium on sedation and anxiety and stress response of tracheal intubation in patients undergoing functional endoscopic sinus surgery., Methods: One hundred twenty patients undergoing endoscopic sinus surgery were randomly divided into four groups: group DP, group D, group P and group N. The blood pressure (BP), heart rate (HR), blood oxygen saturation (SPO2), EEG, bispectral index (BIS), Ramsay sedation score and state anxiety questionnaire (SAI) were recorded before administration (T0), 10 min (T1), 20 min (T2) and 30 min (T3) after administration. After 30 min, endotracheal intubation was performed after anesthesia induction. The BP, HR, SPO2 were recorded 1 min before intubation (T4), intubation (T5), 3 min (T6) after intubation, 5 min (T7) after intubation, and blood samples were collected from patients before administration and after intubation 2 min to detect serum cortisol (Cor), adrenalin (E) norepinephrine (NE) and blood glucose (BS)., Results: There was no significant difference in Ramsay sedation score before anesthesia, but the Ramsay sedation score in group D、DP was significantly higher than that in group P and group N, the BIS, BP, HR and anxiety scores were significantly lower than those in the group P and group N (p < 0.05). There was no significant difference in Ramsay sedation score, BIS value, anxiety score and BP, HR between group D and group DP (p > 0.05). Compared with T4, there was no significant difference in BIS and BP, HR in group D, group DP and group P (p > 0.05), but the BIS, BP and HR in group N were significantly higher than T4, (p < 0.05). Three minutes after intubation there was no statistical difference in the changes of Cor, E, NE and BS values compared with before intubation in group P and group DP (p > 0.05), but the changes of Cor, E, NE and BS values were significantly lower than that in group N (p < 0.05). Compared with T0, the values of NE, E, Cor, BS decreased in group D, DP and P at T4, group DP decreased more significantly than group D (p < 0.05). while the NE, E, Cor, BS of T6 are at the same level as the base value. In group N, the NE, E, Cor, BS of T4 were at the same level of T0, but significantly higher at T6.And at T6, NE and E in group D, P and N were significantly different from those in group DP (p < 0.05)., Conclusion: Preoperative intravenous infusion of dexmedetomidine combined with parecoxib sodium by functional nasal endoscopy can not only calm and resist anxiety, but also better prevent stress response of endotracheal intubation, which is a safe and effective way of preoperative medication., Trial Registration: ChiCTR-OPN-17010444 . Prospectively registered on 16 January 2017.

In late December 2019, a cluster of cases with 2019 Novel Coronavirus pneumonia (SARS-CoV-2) in Wuhan, China, aroused worldwide concern. Previous studies have reported epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19). The purpose of this brief review is to summarize those published studies as of late February 2020 on the clinical features, symptoms, complications, and treatments of COVID-19 and help provide guidance for frontline medical staff in the clinical management of this outbreak.

Background: The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China, has spread rapidly worldwide. In the early stage, we encountered a small but meaningful number of patients who were unintentionally scheduled for elective surgeries during the incubation period of COVID-19. We intended to describe their clinical characteristics and outcomes., Methods: We retrospectively analyzed the clinical data of 34 patients underwent elective surgeries during the incubation period of COVID-19 at Renmin Hospital, Zhongnan Hospital, Tongji Hospital and Central Hospital in Wuhan, from January 1 to February 5, 2020., Findings: Of the 34 operative patients, the median age was 55 years (IQR, 43-63), and 20 (58·8%) patients were women. All patients developed COVID-19 pneumonia shortly after surgery with abnormal findings on chest computed tomographic scans. Common symptoms included fever (31 [91·2%]), fatigue (25 [73·5%]) and dry cough (18 [52·9%]). 15 (44·1%) patients required admission to intensive care unit (ICU) during disease progression, and 7 patients (20·5%) died after admission to ICU. Compared with non-ICU patients, ICU patients were older, were more likely to have underlying comorbidities, underwent more difficult surgeries, as well as more severe laboratory abnormalities (eg, hyperleukocytemia, lymphopenia). The most common complications in non-survivors included ARDS, shock, arrhythmia and acute cardiac injury., Interpretation: In this retrospective cohort study of 34 operative patients with confirmed COVID-19, 15 (44·1%) patients needed ICU care, and the mortality rate was 20·5%., Funding: National Natural Science Foundation of China., Competing Interests: None., (© 2020 The Author(s).)

Objective: To investigate the effects of microRNA-294 (miR-294) on tumor necrosis factor-α (TNF-α), interleukin -6 (IL-6) and high mobility group box 1 (HMGB1) secretion in sepsis by targeting triggering receptor expressed on myeloid cell-1 (TREM-1)., Methods: miRNA-294 was predicted to regulate TREM-1 specially through bioinformatics analysis. Mice macrophage cell lines RAW264.7 were cultured in vitro, the cells were divided into non-inflammatory stage and inflammatory stage, and the cells in the two stages were subdivided into five groups as follows: normal control (NC), NC mimic transfection (NCm), NC inhibitor transfection (NCi), miR-294 mimic transfection (miR-294 m) and miR-294 inhibitor transfection (miR-294i) groups. The ability of miR-294 was confirmed with dual-luciferase activity assay. At non-inflammatory stage, the cells were transfected with mimic or inhibitor of miR-294 or NC using TurboFect™ siRNA Transfection Reagent for 48 hours, mRNA expression of TREM-1 was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). At inflammatory stage, 6 hours after stimulation by lipopolysaccharide (LPS, 1 mg/L), the concentrations of TNF-α, IL-6 and HMGB1 were determined by enzyme linked immunosorbent assay (ELISA), the protein expression of TREM-1 was determined by Western Blot., Results: (1) Dual-luciferase activity assay demonstrated that TREM-1 was the target of miR-294. (2) In non-inflammatory stage, the expression of TREM-1 mRNA (2(-ΔΔCt) ) in miR-294m group was significantly lower than that of the NC and NCm groups (0.673 ± 0.049 vs. 1.000 ± 0.003, 0.915 ± 0.039, t1=2.184, t2=5.421, both P<0.001), the expression of TREM-1 protein (gray scale) was (50.00 ± 1.19)% of NCm group (t=41.586, P<0.001). (3) In inflammatory stage, the concentrations of TNF-α (ng/L) in miR-294 m group was significantly lower than that of the NC group (1 547.18 ± 47.18 vs. 2 702.11 ± 327.20, t=4.212, P=0.010), the concentrations of IL-6 (ng/L) was significantly lower than that of the NC and NCm groups (505.28 ± 33.33 vs. 837.66 ± 69.43, 918.72 ± 119.39, t1=4.382, P1=0.015; t2=5.451, P2=0.021), the level of TREM-1 protein(gray scale) was (51.33 ± 0.88)% of NCm group (t=63.368, P<0.001)., Conclusions: miR-294 reduce TNF-α and IL-6 secretion in LPS-induced RAW264.7 through inhibiting the expression of TREM-1 specifically.

Targeted muscle reinnervation (TMR) technique has been successful in many amputees for providing sufficient electromyography (EMG) signal to control advanced prosthetics. However, it seems to lack further understanding of the recovery progress of muscle functions after targeted muscle reinneveration surgery. In this study, a rat TMR model was developed to investigate intramuscular EMG activity changes after reinnervation. Using the discrete wavelet decomposition and average rectified algorithm, the recorded EMG showed a gradual improvement in the reinnervated muscle within four weeks. Future work will be performed to further assess the efficiency of reinnveration therapy after the surgery.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P = 0.622 for genotype; P = 0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P = 0.014 for allele and P = 0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P = 0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P < 0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis.

To make full use of electromyography (EMG) that contains rich information of muscular activities in active rehabilitation for motor hemiparetic patients, a couple of recent studies have explored the feasibility of applying pattern recognition technique to the classification of multiple motion classes for stroke survivors and reported some promising results. However, it still remains unclear if kinematics signals could also bring good motion classification performance, particularly for patients after traumatic brain damage. In this study, the kinematics signals was used for motion classification analysis in three stroke survivors and two patients after traumatic brain injury, and compared with EMG. The results showed that an average classification error of 7.9 ± 6.8% for the affected arm over all subjects could be achieved with a linear classifier when they performed multiple fine movements, 7.9% lower than that when using EMG. With either kind of signals, the motor control ability of the affected arm degraded significantly in comparison to the intact side. The preliminary results suggested the great promise of kinematics information as well as the biological signals in detecting user's conscious effort for robot-aided active rehabilitation.

Continuous treatment with organic nitrates causes nitrate tolerance and endothelial dysfunction, which is involved with protein kinase C (PKC) signal pathway and NADPH oxidase activation. We determined whether chronic administration with nitroglycerine compromises the protective effects of propofol against tumor necrosis factor (TNF-) induced toxicity in endothelial cells by PKC- β2 dependent NADPH oxidase activation. Primary cultured human umbilical vein endothelial cells were either treated or untreated with TNF- α (40 ng/mL) alone or in the presence of the specific PKC- β2 inhibitor CGP53353 (1 μM)), nitroglycerine (10 μM), propofol (100 μM), propofol plus nitroglycerin, or CGP53353 plus nitroglycerine, respectively, for 24 hours. TNF-α increased the levels of superoxide, Nox (nitrate and nitrite), malondialdehyde, and nitrotyrosine production, accompanied by increased protein expression of p-PKC-β2, gP91phox, and endothelial cell apoptosis, whereas all these changes were further enhanced by nitroglycerine. CGP53353 and propofol, respectively, reduced TNF-α induced oxidative stress and cell toxicity. CGP53353 completely prevented TNF- α induced oxidative stress and cell toxicity in the presence or absence of nitroglycerine, while the protective effects of propofol were neutralized by nitroglycerine. It is concluded that nitroglycerine comprises the protective effects of propofol against TNF-α stimulation in endothelial cells, primarily through PKC-β2 dependent NADPH oxidase activation.