Plasma Proteomics Identify Biomarkers and Pathogenesis of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis. However, little is known about the pathogenesis and biomarkers of COVID-19. Here, we profiled host responses to COVID-19 by performing plasma proteomics of a cohort of COVID-19 patients, including non-survivors and survivors recovered from mild or severe symptoms, and uncovered numerous COVID-19-associated alterations of plasma proteins. We developed a machine-learning-based pipeline to identify 11 proteins as biomarkers and a set of biomarker combinations, which were validated by an independent cohort and accurately distinguished and predicted COVID-19 outcomes. Some of the biomarkers were further validated by enzyme-linked immunosorbent assay (ELISA) using a larger cohort. These markedly altered proteins, including the biomarkers, mediate pathophysiological pathways, such as immune or inflammatory responses, platelet degranulation and coagulation, and metabolism, that likely contribute to the pathogenesis. Our findings provide valuable knowledge about COVID-19 biomarkers and shed light on the pathogenesis and potential therapeutic targets of COVID-19.

NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression.

Impairment of innate immune cell function and metabolism underlies immunosuppression in sepsis; however, a promising therapy to orchestrate this impairment is currently lacking. In this study, high levels of NOD-like receptor family CARD domain containing-3 (NLRC3) correlated with the glycolytic defects of monocytes/macrophages from septic patients and mice that developed immunosuppression. Myeloid-specific NLRC3 deletion improved macrophage glycolysis and sepsis-induced immunosuppression. Mechanistically, NLRC3 inhibits nuclear factor (NF)-κB p65 binding to nuclear factor of activated T cells 5 (NFAT5), which further controls the expression of glycolytic genes and proinflammatory cytokines of immunosuppressive macrophages. This is achieved by decreasing NF-κB activation-co-induced by TNF-receptor-associated factor 6 (TRAF6) or mammalian target of rapamycin (mTOR)-and decreasing transcriptional co-activator p300 activity by inducing NLRC3 sequestration of mTOR and p300. Genetic inhibition of NLRC3 disrupted the NLRC3-mTOR-p300 complex and enhanced NF-κB binding to the NFAT5 promoter in concert with p300. Furthermore, intrapulmonary delivery of recombinant adeno-associated virus harboring a macrophage-specific NLRC3 deletion vector significantly improved the defense of septic mice that developed immunosuppression upon secondary intratracheal bacterial challenge. Collectively, these findings indicate that NLRC3 mediates critical aspects of innate immunity that contribute to an immunocompromised state during sepsis and identify potential therapeutic targets.

Muscular Function Recovery from General Anesthesia in 132 Patients Undergoing Surgery with Acceleromyography, Combined Acceleromyography, and Ultrasonography, and without Monitoring Muscular Function.

BACKGROUND Diaphragmatic thickness fraction (DTF), measured by ultrasound, can predict the occurrence of postoperative residual neuromuscular blockade (RNMB). We hypothesized that the utilization of diaphragmatic ultrasound during the postoperative awakening phase of anesthesia in patients offers a successful means of avoiding RNMB in a notably comfortable manner, as compared to the use of acceleromyograph. MATERIAL AND METHODS Patients who underwent elective thyroid cancer radical surgery were enrolled in this prospective clinical study. Eligible participants were randomly assigned to 1 of 3 groups: 1) combined ultrasonography with acceleromyography group (the US+AMG group), 2) the AMG group, or 3) the usual clinical practice group (the UCP group). The primary outcomes of the study were the incidence of RNMB and hypoxemia after tracheal extubation. RESULTS The study included a total of 127 patients (43 in the US+AMG group, 44 in the AMG group, and 40 in the UCP group). The incidence of RNMB and hypoxemia was higher in the UCP group than in the US+AMG and AMG groups at 15 and 30 min after extubation, respectively. The mean area under the receiver operating characteristic curve, and the decision curve of the recovery rate of DTF (DTF) was greater than that of DTF. CONCLUSIONS The use of diaphragm ultrasound during the postoperative awakening phase of anesthesia can significantly reduce the incidence of RNMB. This method was non-inferior to the use of AMG during the entire perioperative period.

Osteopontin: A Novel Therapeutic Target for Respiratory Diseases.

Osteopontin (OPN) is a multifunctional phosphorylated protein that is involved in physiological and pathological events. Emerging evidence suggests that OPN also plays a critical role in the pathogenesis of respiratory diseases. OPN can be produced and secreted by various cell types in lungs and overexpression of OPN has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. OPN exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis of these respiratory diseases, and genetic and pharmacological moudulation of OPN exerts therapeutic effects in the treatment of respiratory diseases. In this review, we summarize the recent evidence of multifaceted roles and underlying mechanisms of OPN in these respiratory diseases, and targeting OPN appears to be a potential therapeutic intervention for these diseases.

Emerging Roles of Galectin-3 in Pulmonary Diseases.

Galectin-3 is a multifunctional protein that is involved in various physiological and pathological events. Emerging evidence suggests that galectin-3 also plays a critical role in the pathogenesis of pulmonary diseases. Galectin-3 can be produced and secreted by various cell types in the lungs, and the overexpression of galectin-3 has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. Galectin-3 exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis in these pulmonary disorders, and genetic and pharmacologic modulation of galectin-3 has therapeutic effects on the treatment of pulmonary illnesses. In this review, we summarize the structure and function of galectin-3 and the underlying mechanisms of galectin-3 in pulmonary disease pathologies; we also discuss preclinical and clinical evidence regarding the therapeutic potential of galectin-3 inhibitors in these pulmonary disorders. Additionally, targeting galectin-3 may be a very promising therapeutic approach for the treatment of pulmonary diseases.

Notch signaling pathway: a new target for neuropathic pain therapy.

The Notch gene, a highly evolutionarily conserved gene, was discovered approximately 110 years ago and has been found to play a crucial role in the development of multicellular organisms. Notch receptors and their ligands are single-pass transmembrane proteins that typically require cellular interactions and proteolytic processing to facilitate signal transduction. Recently, mounting evidence has shown that aberrant activation of the Notch is correlated with neuropathic pain. The activation of the Notch signaling pathway can cause the activation of neuroglia and the release of pro-inflammatory factors, a key mechanism in the development of neuropathic pain. Moreover, the Notch signaling pathway may contribute to the persistence of neuropathic pain by enhancing synaptic transmission and calcium inward flow. This paper reviews the structure and activation of the Notch signaling pathway, as well as its potential mechanisms of action, to provide novel insights for future treatments of neuropathic pain.

Emerging roles of mechanosensitive ion channels in acute lung injury/acute respiratory distress syndrome.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a devastating respiratory disorder with high rates of mortality and morbidity, but the detailed underlying mechanisms of ALI/ARDS remain largely unknown. Mechanosensitive ion channels (MSCs), including epithelial sodium channel (ENaC), Piezo channels, transient receptor potential channels (TRPs), and two-pore domain potassium ion (K2P) channels, are highly expressed in lung tissues, and the activity of these MSCs can be modulated by mechanical forces (e.g., mechanical ventilation) and other stimuli (e.g., LPS, hyperoxia). Dysfunction of MSCs has been found in various types of ALI/ARDS, and MSCs play a key role in regulating alveolar fluid clearance, alveolar epithelial/endothelial barrier function, the inflammatory response and surfactant secretion in ALI/ARDS lungs. Targeting MSCs exerts therapeutic effects in the treatment of ALI/ARDS. In this review, we summarize the structure and functions of several well-recognized MSCs, the role of MSCs in the pathogenesis of ALI/ARDS and recent advances in the pharmacological and molecular modulation of MSCs in the treatment of ALI/ARDS. According to the current literature, targeting MSCs might be a very promising therapeutic approach against ALI/ARDS.

The pathogenesis and therapeutic strategies of heat stroke-induced liver injury.

Heat stroke (HS) is a life-threatening systemic disease characterized by an elevated core body temperature of more than 40 â„ƒ and subsequent multiple organ dysfunction syndrome. With the growing frequency of global heatwaves, the incidence rate of HS has increased significantly, which has caused a huge burden on people's lives and health. Liver injury is a well-documented complication of HS and usually constitutes the direct cause of patient death. In recent years, a lot of research has been carried out on the pathogenesis and treatment strategies of HS-induced liver injury. In this review, we summarized the important pathogenesis of HS-induced liver injury that has been confirmed so far. In addition to the comprehensive effect of systemic factors such as heat cytotoxicity, coagulopathy, and systemic inflammatory response syndrome, excessive hepatocyte cell pyroptosis, dysfunction of Kupffer cells, abnormal expression of heat shock protein expression, and other factors are also involved in the pathogenesis of HS-induced liver injury. Furthermore, we have also established the current therapeutic strategies for HS-induced liver injury. Our study is of great significance in promoting the understanding of the pathogenesis and treatment of HS-induced liver injury.

Preoperative Anxiety in Chinese Adult Patients Undergoing Elective Surgeries: A Multicenter Cross-Sectional Study.

BACKGROUND: Preoperative anxiety is associated with increased use of anesthetics and poorer postoperative outcomes. However, the prevalence of preoperative anxiety has not been characterized in Chinese patients. In this study, we aimed to estimate the overall prevalence of preoperative anxiety in Chinese adult patients and to explore the sociodemographic and clinical factors associated with preoperative anxiety in China. METHODS: This study was a multicenter cross-sectional study conducted at 32 tertiary referral centers in China from September 1 to October 31, 2020. Adult patients scheduled for elective surgery were evaluated by the 7-item Perioperative Anxiety Scale (PAS-7) for preoperative anxiety after entrance to the operating zone. RESULTS: A total of 5191 patients were recruited, and 5018 of them were analyzed. The prevalence of preoperative anxiety measured by PAS-7 was 15.8% (95% CI 14.8 to 16.9%). Multivariable analyses showed female sex, younger age, non-retired, first in a lifetime surgery, surgery of higher risk, and poorer preoperative sleep were associated with higher prevalence of preoperative anxiety. CONCLUSIONS: Preoperative anxiety was relatively common (prevalence of 15.8%) among adult Chinese patients undergoing elective surgeries. Further studies are needed using suitable assessment tools to better characterize preoperative anxiety, and additional focus should be placed on perioperative education and intervention, especially in primary hospitals. TRIAL REGISTRATION: This study was registered prospectively at www.chictr.org.cn (ChiCTR1900027639) on November 22, 2019.

Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial-mesenchymal transition inhibition in vitro and in vivo.

Epithelial-mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. This study aims to investigate the effects of valproic acid (VPA) on EMT in vitro and in vivo. In vitro, EMT was induced by the administration of transforming growth factor-ß1 (TGF-ß1) in a human alveolar epithelial cell line (A549). The dose effects of VPA (0.1-3 mM) on EMT were subsequently evaluated at different timepoints. VPA (1 mM) was applied prior to the administration of TGF-ß1 and the expression of E-cadherin, vimentin, p-Smad2/3 and p-Akt was assessed. In addition, the effects of a TGF-ß type I receptor inhibitor (A8301) and PI3K-Akt inhibitor (LY294002) on EMT were evaluated. In vivo, the effects of VPA on bleomycin-induced lung fibrosis were evaluated by assessing variables such as survival rate, body weight and histopathological changes, whilst the expression of E-cadherin and vimentin in lung tissue was also evaluated. A8301 and LY294002 were used to ascertain the cellular signaling pathways involved in this model. The administration of VPA prior to TGF-ß1 in A549 cells prevented EMT in both a time- and concentration-dependent manner. Pretreatment with VPA downregulated the expression of both p-Smad2/3 and p-Akt. A8301 administration increased the expression of E-cadherin and reduced the expression of vimentin. LY294002 inhibited Akt phosphorylation induced by TGF-ß1 but failed to prevent EMT. Pretreatment with VPA both increased the survival rate and prevented the loss of body weight in mice with pulmonary fibrosis. Interestingly, both VPA and A8301 prevented EMT and facilitated an improvement in lung structure. Overall, pretreatment with VPA attenuated the development of pulmonary fibrosis by inhibiting EMT in mice, which was associated with Smad2/3 deactivation but without Akt cellular signal involvement.

MicroRNA-155: Regulation of Immune Cells in Sepsis.

MicroRNAs are small noncoding RNAs which regulate gene expression at the posttranscriptional level. miR-155 is encoded by the miR-155 host gene (miR155HG), also known as the noncoding B cell integration cluster (BIC). MicroRNAs are widely expressed in various hematopoietic cells and are involved in regulating the immune system. In this review, we summarized how miR-155 modulates specific immune cells and the regulatory role of miR-155 in sepsis. miR-155 is expressed by different populations of innate and adaptive immune cells and is involved in the regulation of development, proliferation, and function in these cells. Sepsis is associated with uncontrollable inflammatory responses, accompanied by unacceptably high mortality. Due to the inadequacy of diagnostic markers as well as treatment strategies, treating sepsis can be a huge challenge. So far, a large number of experiments have shown that the expression of miR-155 is increased at an early stage of sepsis and that this increase is positively correlated with disease progression and severity. In addition, by blocking the proinflammatory effects of miR-155, it can effectively improve sepsis-related organ injury, providing novel insights to identify potential biomarkers and therapeutic targets for sepsis. However, since most of the current research is limited to animal experiments, further clinical research is required to determine the function of miR-155 and its mechanism related to sepsis.

The impact of carbon monoxide on years of life lost and modified effect by individual- and city-level characteristics: Evidence from a nationwide time-series study in China.

Ambient carbon monoxide (CO) has been linked with mortality and morbidity. Little evidence is available regarding the relation between CO and years of life lost (YLL). Using data from 48 major cities in China from 2013 to 2017, we applied generalized additive models and random effects meta-analyses to explore the effects of CO on YLL from various diseases. Stratified analyses and meta-regression were performed to estimate potential effect modifications of demographic factors, regions, meteorological factors, co-pollutants, urbanization rate, economic level and health service level. Additional life gains due to avoidable YLL under certain scenario were also evaluated. Results indicated that a 1-mg/m³ increase of CO concentrations (lagged over 0-3 d), was associated with 2.08% (95% confidence interval [CI], 1.35%, 2.80%), 2.35% (95% CI: 1.39%, 3.30%), 1.47% (95% CI: -0.01%, 2.93%), 2.28% (95% CI: 1.09%, 3.47%), 2.42% (95% CI: 1.31%, 3.54%), 2.09% (95% CI: 0.47%, 3.72%) increments in daily YLL from non-accidental causes, cardiovascular diseases, respiratory diseases, coronary heart disease, stroke and chronic obstructive pulmonary disease, respectively. These associations were robust to the adjustment of co-pollutants and varied substantially by geography and demographic characteristics. Associations were stronger in the elder people (≥65 years), females, population with low education attainment, and lived in south region, than younger people, males, high educated populations and those lived in north region. Moreover, the harmful impact of increasing CO concentration could be attenuated by city-level characteristics, including the growth of urbanization rate, gross domestic product (GDP), GDP per capita, number of hospital beds, doctors and hospitals. Finally, an estimated life of 0.081 (95% CI: -0.027, 0.190) years would be gained per deceased people if CO concentration could fall to 1 mg/m3. In conclusions, this nationwide analysis showed significant associations between short-term CO exposure and cause-specific YLL. The heterogeneity of both individual- and city-level characteristics should be considered for relevant intervention. These findings may have significant public health implications for the reduction of CO-attributed disease burden in China.

The relationship between core temperature and perioperative shivering during caesarean section under intrathecal anesthesia with bupivacaine and ropivacaine: a randomized controlled study.

PURPOSE: To assess the incidence rate of perioperative shivering for cesarean section and explore the associations between the occurrence of shivering and hypothermia, core temperature change, local anesthetic. METHODS: This is a prospective, randomized, controlled, double-blinded study of 100 patients consenting for caesarean section under intrathecal anesthesia. Parturients with ASA I or II accepted elective caesarean section with combined spinal-epidural anesthesia (SA). 2-2.5 ml of 0.5% bupivacaine or 0.5% ropivacaine was intrathecally injected in group B and group R, respectively. RESULTS: The intraoperative shivering incidence in group B was significantly higher than that in group R (66.7 vs. 20.5%, Pvalue < 0.001), and shivering intensity in group B was significantly greater than group R (score: 1.4 vs. 0.3, Pvalue < 0.001). The core temperature in both groups gradually decreased with the time after SA. Hypothermia (core temperature < 36.0 â„ƒ) 5-30 min after SA was not associated with shivering. However, changes of temperature at 25 and 30 min after SA, and bupivacaine were statistically associated with shivering, with the odds of 10.77 (95% CI: 1.36-85.21, P value = 0.02), 8.88 (95% CI: 1.29-60.97, P value = 0.03), and 7.78 (95% CI: 2.94-20.59, P value < 0.01), respectively. CONCLUSIONS: In our study, for cesarean section, the occurrence of shivering was associated with the local anesthetics and the change of core temperature after SA, while not the hypothermia.

Ethnic disparities in postpartum hemorrhage after cesarean delivery: a retrospective case-control study.

PURPOSE: To explore the relationship of ethnicity and postpartum hemorrhage (PPH) for women who underwent cesarean delivery (CD) and examine the risk factors for PPH in distinct ethnic groups in China. METHODS: We conducted case-control studies with the maternity data from the 11,778 CD cases, in Xinjiang Uygur Autonomous Region. Initially, multivariable logistic regression was used to estimate the disparity of race-ethnicity on the risk of PPH in ethnic Han, Uygur, Hui and Kazakh. Then, we performed case-control studies within two major ethnic groups, identifying the specific risk factors for PPH. RESULTS: Ethnic Uygur were associated with a statistically significant increased odds [adjusted odds ratios (aOR) 2.05; 95% confidence interval (CI) 1.26-3.33] of PPH compared with ethnic Han. For subgroup analyses, in Uygur subgroup, general anesthesia (aOR 7.78; 95% CI 2.31-26.20); placenta previa (aOR 11.18; 95% CI 3.09-40.45); prenatal anemia (aOR 4.84; 95% CI 2.44-9.60); emergency surgery (aOR 4.22; 95% CI 1.95-9.13) were independently associated with PPH. In Han subgroup, general anesthesia (aOR 5.70; 95% CI 1.89-17.26); placenta previa (aOR 20.08; 95% CI 6.35-63.46); multiple pregnancy (aOR 7.21; 95% CI 1.61-32.37); body mass index (aOR 1.19; 95% CI 1.07-1.31) were the risk factors to PPH. CONCLUSION: Uygur have more tendency to PPH compared to Han, and risk factors for PPH in Uygur and Han groups may differ. Knowing these differences may be meaningful when planning interventions and resources for high-risk patients undergoing cesarean delivery, and we need more research aimed at risk factors for PPH.

Maresin1 ameliorates sepsis-associated lung injury by inhibiting the activation of the JAK2/STAT3 and MAPK/ NF-κB signaling pathways.

Sepsis-associated acute lung injury (ALI) is a clinically critical disease that carries a high mortality rate. The pathogenesis of sepsis-associated ALI has not yet been precisely elucidated and there is a lack of effective treatment. As a new endogenous docosahexaenoic acid (DHA)-derived lipid mediators, Maresin1 has a significant dual role of anti-inflammatory and promoting inflammation regression. In this study, we established the sepsis model by the cecal ligation and puncture method (CLP) to explore the effect of Maresin1 on sepsis-induced lung injury. We found that the intervention of Maresin1 could significantly attenuate the sepsis-induced inflammatory responses, characterized by the down-regulation of the level of IL-1ß, IL-6, TNF-α, MPO, etc. Maresin1 could also significantly decrease the number of neutrophils in lung tissue, thus improving the related lung injury indicators. Our experiment clarified that the protective effect of Maresin1 on sepsis-associated lung injury is closely related to its inhibition function of JAK2/STAT3 and MAPK/NF-κB signaling pathways. Our findings provide new research directions and therapeutic targets for sepsis-associated ALI.

Death-associated Protein Kinase 1 Mediates Ventilator-induced Lung Injury in Mice by Promoting Alveolar Epithelial Cell Apoptosis.

BACKGROUND: Alveolar epithelial cell apoptosis is implicated in the onset of ventilator-induced lung injury. Death-associated protein kinase 1 (DAPK1) is associated with cell apoptosis. The hypothesis was that DAPK1 participates in ventilator-induced lung injury through promoting alveolar epithelial cell apoptosis. METHODS: Apoptosis of mouse alveolar epithelial cell was induced by cyclic stretch. DAPK1 expression was altered (knockdown or overexpressed) in vitro by using a small interfering RNA or a plasmid, respectively. C57/BL6 male mice (n = 6) received high tidal volume ventilation to establish a lung injury model. Adeno-associated virus transfection of short hairpin RNA and DAPK1 inhibitor repressed DAPK1 expression and activation in lungs, respectively. The primary outcomes were alveolar epithelial cell apoptosis and lung injury. RESULTS: Compared with the control group, the 24-h cyclic stretch group showed significantly higher alveolar epithelial cell apoptotic percentage (45 ± 4% fold vs. 6 ± 1% fold; P < 0.0001) and relative DAPK1 expression, and this group also demonstrated a reduced apoptotic percentage after DAPK1 knockdown (27 ± 5% fold vs. 53 ± 8% fold; P < 0.0001). A promoted apoptotic percentage in DAPK1 overexpression was observed without stretching (49 ± 6% fold vs. 14 ± 3% fold; P < 0.0001). Alterations in B-cell lymphoma 2 and B-cell lymphoma 2-associated X are associated with DAPK1 expression. The mice subjected to high tidal volume had higher DAPK1 expression and alveolar epithelial cell apoptotic percentage in lungs compared with the low tidal volume group (43 ± 6% fold vs. 4 ± 2% fold; P < 0.0001). Inhibition of DAPK1 through adeno-associated virus infection or DAPK1 inhibitor treatment appeared to be protective against lung injury with reduced lung injury score, resolved pulmonary inflammation, and repressed alveolar epithelial cell apoptotic percentage (47 ± 4% fold and 48 ± 6% fold; 35 ± 5% fold and 34 ± 4% fold; P < 0.0001, respectively). CONCLUSIONS: DAPK1 promotes the onset of ventilator-induced lung injury by triggering alveolar epithelial cell apoptosis through intrinsic apoptosis pathway in mice.

Response of Chinese Anesthesiologists to the COVID-19 Outbreak.

The coronavirus disease 2019, named COVID-19 officially by the World Health Organization (Geneva, Switzerland) on February 12, 2020, has spread at unprecedented speed. After the first outbreak in Wuhan, China, Chinese anesthesiologists encountered increasing numbers of infected patients since December 2019. Because the main route of transmission is via respiratory droplets and close contact, anesthesia providers are at a high risk when responding to the devastating mass emergency. So far, actions have been taken including but not limited to nationwide actions and online education regarding special procedures of airway management, oxygen therapy, ventilation support, hemodynamic management, sedation, and analgesia. As the epidemic situation has lasted for months (thus far), special platforms have also been set up to provide free mental health care to all anesthesia providers participating in acute and critical caring for COVID-19 patients. The current article documents the actions taken, lesson learned, and future work needed.

Maresin1 Promotes M2 Macrophage Polarization Through Peroxisome Proliferator-Activated Receptor-γ Activation to Expedite Resolution of Acute Lung Injury.

BACKGROUND: Acute lung injury (ALI), manifested by progressive hypoxemia and respiratory distress, is associated with high morbidity and mortality, which lacks the effective therapies in clinics. Our previous studies demonstrated that maresin1 (MaR1), a specialized proresolving mediator, could effectively mitigate the inflammation of lipopolysaccharide (LPS)-induced ALI. However, whether MaR1 impacts the macrophage polarization to alleviate ALI remains unclear. Our study explored the effects and underlying mechanisms of MaR1 on the macrophage phenotypes in ALI. MATERIAL AND METHODS: Male BALB/c mice were subjected to endotracheal instillation of LPS to induce ALI and then intravenously injected with MaR1 or normal saline. Intraperitoneal administration of peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibitor GW9662 was given 30 mins before MaR1. We measured the pathohistologic changes, pulmonary edema, inflammatory cytokines, and the flow cytometry of macrophage phenotypes. RESULTS: Our results illustrated that MaR1 ameliorated lung injury and increased monocyte or macrophage recruitment and the release of anti-inflammatory cytokines. The flow cytometry showed that MaR1 promoted polarization of CD11c-CD206+ (M2) macrophages and inhibited polarization of CD11c+CD206- (M1) macrophages. Besides, the western blotting revealed that MaR1 increased the expression of PPAR-γ. The pretreatment with PPAR-γ antagonist GW9662 could significantly suppress the polarization of M2 macrophages and antagonize the protective effects of MaR1 on LPS-stimulated ALI. CONCLUSIONS: MaR1 was able to promote M2 macrophage polarization by reversing LPS-mediated PPAR-γ inhibition, thereby expediting the recovery of LPS-stimulated ALI.

Emergency tracheal intubation in 202 patients with COVID-19 in Wuhan, China: lessons learnt and international expert recommendations.

Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan, China, a panel of international airway management experts discussed the results and formulated consensus recommendations for the management of tracheal intubation in COVID-19 patients. Of 202 COVID-19 patients undergoing emergency tracheal intubation, most were males (n=136; 67.3%) and aged 65 yr or more (n=128; 63.4%). Most patients (n=152; 75.2%) were hypoxaemic (Sao2 <90%) before intubation. Personal protective equipment was worn by all intubating healthcare workers. Rapid sequence induction (RSI) or modified RSI was used with an intubation success rate of 89.1% on the first attempt and 100% overall. Hypoxaemia (Sao2 <90%) was common during intubation (n=148; 73.3%). Hypotension (arterial pressure <90/60 mm Hg) occurred in 36 (17.8%) patients during and 45 (22.3%) after intubation with cardiac arrest in four (2.0%). Pneumothorax occurred in 12 (5.9%) patients and death within 24 h in 21 (10.4%). Up to 14 days post-procedure, there was no evidence of cross infection in the anaesthesiologists who intubated the COVID-19 patients. Based on clinical information and expert recommendation, we propose detailed planning, strategy, and methods for tracheal intubation in COVID-19 patients.

LncRNAMORT is upregulated in myocardial infarction and promotes the apoptosis of cardiomyocyte by downregulating miR-93.

BACKGROUND: Myocardial infarction (MI) affects the expression of a large number of lncRNAs, while the functions of those dysregulated lncRNAs are mostly unclear. MATERIALS AND METHODS: Expression of MORT and miR-93 in hearth tissues and plasma of both MI mice and Sham mice and both MI patients and healthy controls was detected by RT-qPCR. Correlations of expression levels of MORT and miR-93 between hear tissues and plasma of MI mice were explored by performing linear regression. RESULTS: In the present study we found that MORT expression levels were higher, while expression levels of miR-93 were lower in both plasma and heart tissues of mice MI mice models compared with Sham mice. Plasma levels of MORT and miR-93 were largely consistent with expression levels of MORT and miR-93 in heart tissue of MI mice. MORT expression levels were also higher, while levels of miR-93 were also lower in plasma of MI patients compared with healthy controls. MORT and miR-93 were inversely correlated in MI patients but not in healthy controls. MORT overexpression resulted in inhibited miR-93 expression in cardiomyocytes (AC16 cell line), while miR-93 overexpression did not significantly affect MORT expression. MORT overexpression promoted cardiomyocyte apoptosis, while miR-93 overexpression played and opposite role and attenuated the effects of MORT overexpression. CONCLUSION: Therefore, lncRNA MORT is upregulated in myocardial infarction and promotes the apoptosis of cardiomyocyte by downregulating miR-93.