Transcriptional response of USP18 predicts treatment outcomes of interferon-alpha in HBeAg-positive chronic hepatitis B patientsefere.

Ubiquitin-specific protease 18 (USP18) is an important inhibitor of interferon (IFN) antiviral activity, and the aim of this study was to investigate the association between the USP18 mRNA level change in peripheral blood mononuclear cells (PBMCs) when stimulated with IFN in vitro before initiating treatment and the treatment outcomes in HBeAg-positive chronic hepatitis B (CHB) patients treated with IFN. A total of 44 patients who received standard IFN-based anti-HBV therapy and follow-up were enrolled in the study. The in vitro IFN-induced USP18 mRNA change (USP18IFN-N ) was measured via comparison of quantitative PCR-determined USP18 transcription levels of BPMCs cultured with and without IFN stimulation. Either for virological (VR) or serological response (SR), the baseline USP18IFN-N was significantly higher (P = 0.018 for VR, P = 0.008 for SR) among nonresponders (n = 23 for VR, n = 33 for SR) than that of responders (n = 21 for VR, n = 11 for SR). Multivariate analyses revealed baseline USP18IFN-N was a novel independent predictor for either VR (OR = 0.292, 95% CI = 0.102-0.835, P = 0.022) or SR (OR = 0.173, 95% CI = 0.035-0.849, P = 0.031) in our cohort. In addition, baseline USP18IFN-N in combination with HBV DNA loads or HBeAg levels showed improved accuracy of pretreatment prediction for VR or SR responders, respectively. Baseline USP18IFN-N levels are associated with both virological and serological response, and have the potential to become a clinical predictor for treatment outcomes in HBeAg-positive CHB patients before initiating IFN-α therapy

Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT):A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H2O (DCollapse24–6). Patients were classified as low, medium, or high recruiters on the basis of tertiles of DCollapse24–6. Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H2O for low versus medium versus high recruitability (P, 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H2O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension.</p

Hydrodynamic field driving effect and mathematical model construction of water quality formation and evolution in coal mine

The change of regional hydrodynamic field caused by coal mining process affects the multi-field process of the formation and evolution of mine water quality, which may lead to the pollution of the water environment in the coal mining area. Research on the driving mechanism of the hydrodynamic field and the method of quantitative calculation of key parameters is the premise of quantitative description on the multi-field effects of site pollution in the coal mining areas and its corresponding pollution control. Taking the Menkeqing Coal Mine as the geological background, this paper clarifies the evolution mechanism of the hydrodynamic field of goaf water. According to the difference in the flow path of the hydrodynamic field, it is divided into the stages of water level recovery and filling-up. It reveals the complex process of the formation and evolution of water quality in the goaf, with the hydrodynamic field as the main driving force, and the synergistic effects of multiple fields such as the hydrochemical field and the microbial field. Then the concept model of the water level recovery stage and filling-up stage and the theoretical calculation model of the analytical solution of the key parameters (permeability coefficient, water level, and water volume) of the hydrodynamic field are proposed. The measured data of the similar material simulation test and the three-dimensional box simulation test are compared with the model calculation results. The theoretical calculation of the permeability coefficient and the curve of goaf water level with time and the experimental measurement error are about 13.2% and 22.5%, respectively. The reliability of the theoretical calculation model is verified. Finally, on the basis of the equations of the hydrodynamic field, and the hydrochemical field and the microbial field under the influence of the hydrodynamic field in the goaf, a multi-field coupling effect model dominated by the hydrodynamic field is constructed. The constitutive model provides an inspiration for exploring the formation and evolution of coal mine water quality driven by the coupling of hydrodynamic field. This study supplements and expands the theory of coal mine water pollution prevention and control

Sigh in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: the PROTECTION pilot randomized clinical trial

Background: Sigh is a cyclic brief recruitment manoeuvre: previous physiological studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity and increase release of surfactant. Research question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study design and methods: We conducted a multi-center non-inferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or acute respiratory distress syndrome undergoing PSV. Patients were randomized to the No Sigh group and treated by PSV alone, or to the Sigh group, treated by PSV plus sigh (increase of airway pressure to 30 cmH2Ofor 3 seconds once per minute) until day 28 or death or successful spontaneous breathing trial. The primary endpoint of the study was feasibility, assessed as non-inferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiological parameters in the first week from randomization, 28-day mortality and ventilator-free days. Results: Two-hundred fifty-eight patients (31% women; median age 65 [54-75] years) were enrolled. In the Sigh group, 23% of patients failed to remain on assisted ventilation vs. 30% in the No Sigh group (absolute difference -7%, 95%CI -18% to 4%; p=0.015 for non-inferiority). Adverse events occurred in 12% vs. 13% in Sigh vs. No Sigh (p=0.852). Oxygenation was improved while tidal volume, respiratory rate and corrected minute ventilation were lower over the first 7 days from randomization in Sigh vs. No Sigh. There was no significant difference in terms of mortality (16% vs. 21%, p=0.342) and ventilator-free days (22 [7-26] vs. 22 [3-25] days, p=0.300) for Sigh vs. No Sigh. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk

Physical simulation and fine digital study of thermal foam compound flooding

According to the similarity criterion of 3D physical simulation of thermal recovery, experimental parameters of 3D physical simulation of steam flooding and thermal foam compound flooding in extra-heavy oil reservoirs of the Gudao Oilfield were calculated, and relevant experiments were carried out. Based on the experimental results, 3D fine numerical simulation was carried out to analyze the steam flooding and thermal foam compound flooding in heavy oil reservoirs. The results show that thermal foam compound flooding could effectively inhibit steam channeling and improve sweep efficiency, and thus enhance the oil recovery in heavy oil reservoirs after steam flooding. Technological parameters of thermal foam compound flooding were optimized according to the results of fine numerical simulation. The optimum injection method is foam-slug injection, the optimal steam injection rate is 25 mL/min, nitrogen injection rate is 1 000 mL/min (standard conditions), the time of foam-slug injection is 1.0 min and the interval between foam-slugs is about 10-20 min during thermal foam-slug injection. At last, the similarity criterion was employed for inversion calculation of the optimization results. Based on the results, optimal field injection and production parameters can be confirmed. The ultimate recovery ratio of thermal foam compound flooding in super-heavy oil reservoirs could reach 42.15%, which is 12.50% higher than steam flooding. Key words: heavy oil reservoir, thermal foam compound flooding, physical simulation, similarity criterion, numerical simulatio

Characterizing Post-Fire Forest Structure Recovery in the Great Xing’an Mountain Using GEDI and Time Series Landsat Data

Understanding post-fire forest recovery is critical to the study of forest carbon dynamics. Many previous studies have used multispectral imagery to estimate post-fire recovery, yet post-fire forest structural development has rarely been evaluated in the Great Xing’an Mountain. In this study, we extracted the historical fire events from 1987 to 2019 based on a classification of Landsat imagery and assessed post-fire forest structure for these burned patches using Global Ecosystem Dynamics Investigation (GEDI)-derived metrics from 2019 to 2021. Two drivers were assessed for the influence on post-fire structure recovery, these being pre-fire canopy cover (i.e., dense forest and open forest) and burn severity levels (i.e., low, moderate, and high). We used these burnt patches to establish a 25-year chronosequence of forest structural succession by a space-for-time substitution method. Our result showed that the structural indices suggested delayed recovery following the fire, indicating a successional process from the decomposition of residual structures to the regeneration of new tree species in the post-fire forest. Across the past 25-years, the dense forest tends toward greater recovery than open forest, and the recovery rate was faster for low severity, followed by moderate severity and high severity. Specifically, in the recovery trajectory, the recovery indices were 21.7% and 17.4% for dense forest and open forest, and were 27.1%, 25.8%, and 25.4% for low, moderate, and high burn severity, respectively. Additionally, a different response to the fire was found in the canopy structure and height structure since total canopy cover (TCC) and plant area index (PAI) recovered faster than relative height (i.e., RH75 and RH95). Our results provide valuable information on forest structural restoration status, that can be used to support the formulation of post-fire forest management strategies in Great Xing’an Mountain

Nomogram for the prediction of postoperative hypoxemia in patients with acute aortic dissection

Abstract Background Postoperative hypoxemia is quite common in patients with acute aortic dissection (AAD) and is associated with poor clinical outcomes. However, there is no method to predict this potentially life-threatening complication. The study aimed to develop a regression model in patients with AAD to predict postoperative hypoxemia, and to validate it in an independent dataset. Methods All patients diagnosed with AAD from December 2012 to December 2017 were retrospectively screened for potential eligibility. Preoperative and intraoperative variables were included for analysis. Logistic regression model was fit by using purposeful selection procedure. The original dataset was split into training and validating datasets by 4:1 ratio. Discrimination and calibration of the model was assessed in the validating dataset. A nomogram was drawn for clinical utility. Results A total of 211 patients, involving 168 in non-hypoxemia and 43 in hypoxemia group, were included during the study period (incidence: 20.4%). Duration of mechanical ventilation (MV) was significantly longer in the hypoxemia than non-hypoxemia group (41(10.5140) vs. 12(3.75,70.25) hours; p = 0.002). There was no difference in the hospital mortality rate between the two groups. The purposeful selection procedure identified 8 variables including hematocrit (odds ratio [OR]: 0.89, 95% confidence interval [CI]: 0.80 to 0.98, p = 0.011), PaO2/FiO2 ratio (OR: 0.99, 95% CI: 0.99 to 1.00, p = 0.011), white blood cell count (OR: 1.21, 95% CI: 1.06 to 1.40, p = 0.008), body mass index (OR: 1.32, 95% CI: 1.15 to 1.54; p = 0.000), Stanford type (OR: 0.22, 95% CI: 0.06 to 0.66; p = 0.011), pH (OR: 0.0002, 95% CI: 2*10− 8 to 0.74; p = 0.048), cardiopulmonary bypass time (OR: 0.99, 95% CI: 0.98 to 1.00; p = 0.031) and age (OR: 1.03, 95% CI: 0.99 to 1.08; p = 0.128) to be included in the model. In an independent dataset, the area under curve (AUC) of the prediction model was 0.869 (95% CI: 0.802 to 0.936). The calibration was good by visual inspection. Conclusions The study developed a model for the prediction of postoperative hypoxemia in patients undergoing operation for AAD. The model showed good discrimination and calibration in an independent dataset that was not used for model training

Systemic cytokines inhibition with Imp7 siRNA nanoparticle ameliorates gut injury in a mouse model of ventilator-induced lung injury

Mechanical ventilation (MV) may negatively affect the lungs and cause the release of inflammatory mediators, resulting in extra-pulmonary organ dysfunction. Studies have revealed systemically elevated levels of proinflammatory cytokines in animal models of ventilator-induced lung injury (VILI); however, whether these cytokines have an effect on gut injury and the mechanisms involved remain unknown. In this study, VILI was generated in mice with high tidal volume mechanical ventilation (20 ml/kg). Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 concentrations in serum and gut measured by ELISA showed significant elevation in the VILI mice. Significant increases in gut injury and PANoptosis were observed in the VILI mice, which were positively correlated with the serum levels of TNF-α, IL-1β, and IL-6. The VILI mice displayed intestinal barrier defects, decreased expressions of occludin and zonula occludin-1 (ZO-1), and increased expression of claudin-2 and the activation of myosin light chain (MLC). Importantly, intratracheal administration of Imp7 siRNA nanoparticle effectively inhibited cytokines production and protected mice from VILI-induced gut injury. These data provide evidence of systemic cytokines contributing to gut injury following VILI and highlight the possibility of targeting cytokines inhibition via Imp7 siRNA nanoparticle as a potential therapeutic intervention for alleviating gut injury following VILI