Homotherapy for heteropathy: Interleukin-41 and its biological functions.

Interleukin-41 (IL-41) is a newly discovered cytokine, named Cometin, Subfatin, meteorin-like transcription (Metrnl), and so forth. It is widely expressed in animals and can exert its biological roles through autocrine and paracrine forms. It has functions such as anti-inflammatory, improving body metabolism, regulating immunity, regulating fat metabolism and participates in the process of autoimmune disease or inflammatory injury. It plays an important role in psoriasis, diabetes, Crohn's disease (CD), osteoarthritis, Kawasaki disease (KD), Graves' disease, autoimmune hepatitis, infertility, obesity, sepsis, cardiovascular diseases and respiratory diseases. This paper reviews the biological functions of IL-41, the relationship between IL-41 and diseases, the effects of IL-41 in the cytokine network and the possible signalling pathways. In order to explore the same target or the same drug for the treatment of different diseases from the perspective of homotherapy for heteropathy, cytokine strategies based on IL-41 have been put forward for the precise treatment of immune diseases and inflammatory diseases. It is worth noting that IL-41 related preparations for lung protection and smoking cessation are interesting research fields.

Congenital diaphragmatic hernia: quality improvement using a maximal lung protection strategy and early surgery-improved survival.

To evaluate the effectiveness of a novel protocol, adopted in our institution, as a quality improvement project for congenital diaphragmatic hernia (CDH). A maximal lung protection (MLP) protocol was implemented in 2019. This strategy included immediate use of high-frequency oscillatory ventilation (HFOV) after birth, during the stay at the Neonatal Intensive Care Unit (NICU), and during surgical repair. HFOV strategy included low distending pressures and higher frequencies (15 Hz) with subsequent lower tidal volumes. Surgical repair was performed early, within 24 h of birth, if possible. A retrospective study of all inborn neonates prenatally diagnosed with CDH and without major associated anomalies was performed at the NICU of Schneider Children's Medical Center of Israel between 2009 and 2022. Survival rates and pulmonary outcomes of neonates managed with MLP were compared to the historical standard care cohort. Thirty-three neonates were managed with the MLP protocol vs. 39 neonates that were not. Major adverse outcomes decreased including death rate from 46 to 18% (p = 0.012), extracorporeal membrane oxygenation from 39 to 0% (p < 0.001), and pneumothorax from 18 to 0% (p = 0.013). CONCLUSION:  MLP with early surgery significantly improved survival and additional adverse outcomes of neonates with CDH. Prospective randomized studies are necessary to confirm the findings of the current study. WHAT IS KNOWN: • Ventilator-induced lung injury was reported as the main cause of mortality in neonates with congenital diaphragmatic hernia (CDH). • Conventional ventilation is recommended by the European CDH consortium as the first-line ventilation modality; timing of surgery is controversial. WHAT IS NEW: • A maximal lung protection strategy based on 15-Hz high-frequency oscillatory ventilation with low distending pressures as initial modality and early surgery significantly reduced mortality and other outcomes.

Single-cell transcriptome atlas reveals protective characteristics of COVID-19 mRNA vaccine.

Messenger RNA (mRNA) vaccines are promising alternatives to conventional vaccines in many aspects. We previously developed a lipopolyplex (LPP)-based mRNA vaccine (SW0123) that demonstrated robust immunogenicity and strong protective capacity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in mice and rhesus macaques. However, the immune profiles and mechanisms of pulmonary protection induced by SW0123 remain unclear. Through high-resolution single-cell analysis, we found that SW0123 vaccination effectively suppressed SARS-CoV-2-induced inflammatory responses by inhibiting the recruitment of proinflammatory macrophages and increasing the frequency of polymorphonuclear myeloid-derived suppressor cells. In addition, the apoptotic process in both lung epithelial and endothelial cells was significantly inhibited, which was proposed to be one major mechanism contributing to vaccine-induced lung protection. Cell-cell interaction in the lung compartment was also altered by vaccination. These data collectively unravel the mechanisms by which the SW0123 protects against lung damage caused by SARS-CoV-2 infection.

Practical assessment of risk of VILI from ventilating power: a conceptual model.

At the bedside, assessing the risk of ventilator-induced lung injury (VILI) requires parameters readily measured by the clinician. For this purpose, driving pressure (DP) and end-inspiratory static 'plateau' pressure ([Formula: see text]) of the tidal cycle are unquestionably useful but lack key information relating to associated volume changes and cumulative strain. 'Mechanical power', a clinical term which incorporates all dissipated ('non-elastic') and conserved ('elastic') energy components of inflation, has drawn considerable interest as a comprehensive 'umbrella' variable that accounts for the influence of ventilating frequency per minute as well as the energy cost per tidal cycle. Yet, like the raw values of DP and [Formula: see text], the absolute levels of energy and power by themselves may not carry sufficiently precise information to guide safe ventilatory practice. In previous work we introduced the concept of 'damaging energy per cycle'. Here we describe how-if only in concept-the bedside clinician might gauge the theoretical hazard of delivered energy using easily observed static circuit pressures ([Formula: see text] and positive end expiratory pressure) and an estimate of the maximally tolerated (threshold) non-dissipated ('elastic') airway pressure that reflects the pressure component applied to the alveolar tissues. Because its core inputs are already in use and familiar in daily practice, the simplified mathematical model we propose here for damaging energy and power may promote deeper comprehension of the key factors in play to improve lung protective ventilation.

Effect of pressure-controlled ventilation-volume guaranteed mode combined with individualized positive end-expiratory pressure on respiratory mechanics, oxygenation and lung injury in patients undergoing laparoscopic surgery in Trendelenburg position.

The study aimed to investigate the efficacy of PCV-VG combined with individual PEEP during laparoscopic surgery in the Trendelenburg position. 120 patients were randomly divided into four groups: VF group (VCV plus 5cmH2O PEEP), PF group (PCV-VG plus 5cmH2O PEEP), VI group (VCV plus individual PEEP), and PI group (PCV-VG plus individual PEEP). Pmean, Ppeak, Cdyn, PaO2/FiO2, VD/VT, A-aDO2 and Qs/Qt were recorded at T1 (15 min after the induction of anesthesia), T2 (60 min after pneumoperitoneum), and T3 (5 min at the end of anesthesia). The CC16 and IL-6 were measured at T1 and T3. Our results showed that the Pmean was increased in VI and PI group, and the Ppeak was lower in PI group at T2. At T2 and T3, the Cdyn of PI group was higher than that in other groups, and PaO2/FiO2 was increased in PI group compared with VF and VI group. At T2 and T3, A-aDO2 of PI and PF group was reduced than that in other groups. The Qs/Qt was decreased in PI group compared with VF and VI group at T2 and T3. At T2, VD/VT in PI group was decreased than other groups. At T3, the concentration of CC16 in PI group was lower compared with other groups, and IL-6 level of PI group was decreased than that in VF and VI group. In conclusion, the patients who underwent laparoscopic surgery, PCV-VG combined with individual PEEP produced favorable lung mechanics and oxygenation, and thus reducing inflammatory response and lung injury.Clinical Trial registry: chictr.org. identifier: ChiCTR-2100044928.

Bedside calculation of mechanical power during volume- and pressure-controlled mechanical ventilation.

BACKGROUND: Mechanical power (MP) is the energy delivered to the respiratory system over time during mechanical ventilation. Our aim was to compare the currently available methods to calculate MP during volume- and pressure-controlled ventilation, comparing different equations with the geometric reference method, to understand whether the easier to use surrogate formulas were suitable for the everyday clinical practice. This would warrant a more widespread use of mechanical power to promote lung protection. METHODS: Forty respiratory failure patients, sedated and paralyzed for clinical reasons, were ventilated in volume-controlled ventilation, at two inspiratory flows (30 and 60 L/min), and pressure-controlled ventilation with a similar tidal volume. Mechanical power was computed both with the geometric method, as the area between the inspiratory limb of the airway pressure and the volume, and with two algebraic methods, a comprehensive and a surrogate formula. RESULTS: The bias between the MP computed by the geometric method and by the comprehensive algebraic method during volume-controlled ventilation was respectively 0.053 (0.77, - 0.81) J/min and - 0.4 (0.70, - 1.50) J/min at low and high flows (r2 = 0.96 and 0.97, p < 0.01). The MP measured and computed by the two methods were highly correlated (r2 = 0.95 and 0.94, p < 0.01) with a bias of - 0.0074 (0.91, - 0.93) and - 1.0 (0.45, - 2.52) J/min at high-low flows. During pressure-controlled ventilation, the bias between the MP measured and the one calculated with the comprehensive and simplified methods was correlated (r2 = 0.81, 0.94, p < 0.01) with mean differences of - 0.001 (2.05, - 2.05) and - 0.81 (2.11, - 0.48) J/min. CONCLUSIONS: Both for volume-controlled and pressure-controlled ventilation, the surrogate formulas approximate the reference method well enough to warrant their use in the everyday clinical practice. Given that these formulas require nothing more than the variables already displayed by the intensive care ventilator, a more widespread use of mechanical power should be encouraged to promote lung protection against ventilator-induced lung injury.

Evaluation of the intratidal compliance profile at different PEEP levels in children with healthy lungs: a prospective, crossover study.

BACKGROUND: Optimal intraoperative lung protective ventilation (LPV) strategies in young children are largely under-explored. Individualised PEEP levels are likely to contribute to optimal lung protection. We determined optimal PEEP levels in young children during general anaesthesia by evaluating changes in intratidal compliance with varying PEEP. METHODS: Children aged ≤6 yr were enrolled in this prospective interventional study. After induction of general anaesthesia and neuromuscular block (rocuronium), children were randomly assigned to be mechanically ventilated at each of three PEEP levels for 15 min each: 5, 8, and 12 cm H2O PEEP (PEEP5/8/12). Haemodynamic and respiratory data were recorded at each PEEP level. Intratidal volume-compliance was classified into one of six compliance profiles (increasing/decreasing/horizontal [plateau]/increasing-horizontal/horizontal-decreasing/increasing-horizontal-decreasing) at each PEEP level. The primary outcome was intratidal compliance at different PEEP levels. RESULTS: Forty-seven children were enrolled (40% female; median age: 2.5 yr [0.9-3.7]). Mean airway pressure progressively increased from 7.6 cm H2O (0.5) at PEEP5, 10.5 cm H2O (0.9) at PEEP8 to 14.3 cm H2O (0.5) PEEP12 (P<0.001). Mean driving pressure was lower at PEEP12 (6.3 cm H2O [1.1]), compared with PEEP8 (6.5 cm H2O [1.1]) and PEEP5 (7.0 cm H2O [1.5]; P=0.004 for trend). Intratidal compliance increased in 31/47 (66%) children at PEEP5, but was less likely with PEEP8 (9/47; 19.1%) and was absent at PEEP12. At PEEP8, plateaued compliance was most frequent (16/46; 34.8%). At PEEP12, decreasing compliance occurred most frequently (32/46; 69.6%). CONCLUSIONS: Intratidal compliance at different PEEP levels varied widely in young children under general anaesthesia. These data suggest that individualised PEEP levels are required for optimal lung protection in children. CLINICAL TRIAL REGISTRATION: NCT03533296.

Fully automated postoperative ventilation in cardiac surgery patients: a randomised clinical trial.

BACKGROUND: Ensuring that lung-protective ventilation is achieved at scale is challenging in perioperative practice. Fully automated ventilation may be more effective in delivering lung-protective ventilation. Here, we compared automated lung-protective ventilation with conventional ventilation after elective cardiac surgery in haemodynamically stable patients. METHODS: In this single-centre investigator-led study, patients were randomly assigned at the end of cardiac surgery to receive either automated (adaptive support ventilation) or conventional ventilation. The primary endpoint was the proportion of postoperative ventilation time characterised by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first three postoperative hours. Secondary outcomes included severe hypoxaemia (Spo2 <85%) and resumption of spontaneous breathing. Data are presented as mean (95% confidence intervals [CIs]). RESULTS: We randomised 220 patients (30.4% females; age: 62-76 yr). Subjects randomised to automated ventilation (n=109) spent a 29.7% (95% CI: 22.1-37.4) higher mean proportion of postoperative ventilation time receiving optimal postoperative ventilation after surgery (P<0.001) compared with subjects receiving conventional postoperative ventilation (n=111). Automated ventilation also reduced the proportion of postoperative ventilation time that subjects were exposed to injurious ventilatory settings by 2.5% (95% CI: 1-4; P=0.003). Severe hypoxaemia was less likely in subjects randomised to automated ventilation (risk ratio: 0.26 [0.22-0.31]; P<0.01). Subjects resumed spontaneous breathing more rapidly when randomised to automated ventilation (hazard ratio: 1.38 [1.05-1.83]; P=0.03). CONCLUSIONS: Fully automated ventilation in haemodynamically stable patients after cardiac surgery optimised lung-protective ventilation during postoperative ventilation, with fewer episodes of severe hypoxaemia and an accelerated resumption of spontaneous breathing. CLINICAL TRIAL REGISTRATION: NCT03180203.

Effect of a new respiratory care bundle on bronchopulmonary dysplasia in preterm neonates.

The development of devices that can fix the tidal volume in high-frequency oscillatory ventilation (HFOV) has allowed for a significant improvement in the management of HFOV. At our institution, this had led to the earlier use of HFOV and promoted a change in the treatment strategy involving the use of higher frequencies (above 15 Hz) and lower high-frequency tidal volumes (VThf). The purpose of this observational study was to assess how survival without bronchopulmonary dysplasia grades 2 and 3 (SF-BPD) is influenced by these modifications in the respiratory strategy applied to preterm infants (gestational age < 32 weeks at birth) who required mechanical ventilation (MV) in the first 3 days of life. We compared a baseline period (2012-2013) against a period in which this strategy had been fully implemented (2016-2017). A total of 182 patients were exposed to MV in the first 3 days of life being a higher proportion on HFOV at day 3 in the second period 79.5% (n 35) in 2016-2017 vs 55.4% (n 31) in 2012-2013. After adjusting for perinatal risk factors, the second period is associated with an increased rate of SF-BPD (OR 2.28; CI 95% 1.072-4.878); this effect is more evident in neonates born at a gestational age of less than 29 weeks (OR 4.87; 95% CI 1.9-12.48).Conclusions : The early use of HFOV combined with the use of higher frequencies and very low VT was associated with an increase in the study population's SF-BPD. What is Known: • High-frequency ventilation with volume guarantee improve ventilation stability and has been shown to reduce lung damage in animal models. What is New: • The strategy of an earlier use of high-frequency oscillatory ventilation combined with the use of higher frequencies and lower tidal volume is associated to an increase in survival without bronchopulmonary dysplasia in our population of preterm infants.

Low-frequency ventilation during cardiopulmonary bypass for lung protection: A randomized controlled trial.

OBJECTIVE: Pulmonary dysfunction is a common complication in patients undergoing heart surgery. Current clinical practice does not include any specific strategy for lung protection. To compare the anti-inflammatory effects of low-frequency ventilation (LFV), as measured by nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) p65 pathway activation, for the entire cardiopulmonary bypass (CPB) vs both lungs left collapsed in patients undergoing coronary artery bypass grafting (CABG). METHODS: Two groups parallel randomized controlled trial. The primary outcome was inflammation measured by NF-κB p65 activation in pre- and post-CPB lung biopsies. Secondary outcomes were additional inflammatory markers in both biopsy tissue and blood. RESULTS: Thirty-seven patients were randomly allocated to LFV (18) and to both lungs left collapsed (19). The mean concentration of NF-κB p65 in the biopsies before chest closure (adjusted for pre-CPB concentration) was higher in the LFV group compared to both lungs left collapsed group but this was not significant (0.102, 95% confidence interval, -0.022 to 0.226, P = 0.104). There were no significant differences between groups in the other inflammatory markers measured in tissue and blood. CONCLUSIONS: In patients undergoing elective CABG, the use of LFV during CPB when compared to both lungs left collapsed does not seem to reduce inflammation in lung biopsies and blood.

Can EMS Providers Provide Appropriate Tidal Volumes in a Simulated Adult-sized Patient with a Pediatric-sized Bag-Valve-Mask?

INTRODUCTION: In the prehospital setting, Emergency Medical Services (EMS) professionals rely on providing positive pressure ventilation with a bag-valve-mask (BVM). Multiple emergency medicine and critical care studies have shown that lung-protective ventilation protocols reduce morbidity and mortality. Our primary objective was to determine if a group of EMS professionals could provide ventilations with a smaller BVM that would be sufficient to ventilate patients. Secondary objectives included 1) if the pediatric bag provided volumes similar to lung-protective ventilation in the hospital setting and 2) compare volumes provided to the patient depending on the type of airway (mask, King tube, and intubation). METHODS: Using a patient simulator of a head and thorax that was able to record respiratory rate, tidal volume, peak pressure, and minute volume via a laptop computer, participants were asked to ventilate the simulator during six 1-minute ventilation tests. The first scenario was BVM ventilation with an oropharyngeal airway in place ventilating with both an adult- and pediatric-sized BVM, the second scenario had a supraglottic airway and both bags, and the third scenario had an endotracheal tube and both bags. Participants were enrolled in convenience manner while they were on-duty and the research staff was able to travel to their stations. Prior to enrolling, participants were not given any additional training on ventilation skills. RESULTS: We enrolled 50 providers from a large, busy, urban fire-based EMS agency with 14.96 (SD = 9.92) mean years of experience. Only 1.5% of all breaths delivered with the pediatric BVM during the ventilation scenarios were below the recommended tidal volume. A greater percentage of breaths delivered in the recommended range occurred when the pediatric BVM was used (17.5% vs 5.1%, p < 0.001). Median volumes for each scenario were 570.5mL, 664.0mL, 663.0mL for the pediatric BMV and 796.0mL, 994.5mL, 981.5mL for the adult BVM. In all three categories of airway devices, the pediatric BVM provided lower median tidal volumes (p < 0.001). CONCLUSION: The study suggests that ventilating an adult patient is possible with a smaller, pediatric-sized BVM. The tidal volumes recorded with the pediatric BVM were more consistent with lung-protective ventilation volumes.

The association of postoperative pulmonary complications in 109,360 patients with pressure-controlled or volume-controlled ventilation.

We thought that the rate of postoperative pulmonary complications might be higher after pressure-controlled ventilation than after volume-controlled ventilation. We analysed peri-operative data recorded for 109,360 adults, whose lungs were mechanically ventilated during surgery at three hospitals in Massachusetts, USA. We used multivariable regression and propensity score matching. Postoperative pulmonary complications were more common after pressure-controlled ventilation, odds ratio (95%CI) 1.29 (1.21-1.37), p < 0.001. Tidal volumes and driving pressures were more varied with pressure-controlled ventilation compared with volume-controlled ventilation: mean (SD) variance from the median 1.61 (1.36) ml.kg-1 vs. 1.23 (1.11) ml.kg-1 , p < 0.001; and 3.91 (3.47) cmH2 O vs. 3.40 (2.69) cmH2 O, p < 0.001. The odds ratio (95%CI) of pulmonary complications after pressure-controlled ventilation compared with volume-controlled ventilation at positive end-expiratory pressures < 5 cmH2 O was 1.40 (1.26-1.55) and 1.20 (1.11-1.31) when ≥ 5 cmH2 O, both p < 0.001, a relative risk ratio of 1.17 (1.03-1.33), p = 0.023. The odds ratio (95%CI) of pulmonary complications after pressure-controlled ventilation compared with volume-controlled ventilation at driving pressures of < 19 cmH2 O was 1.37 (1.27-1.48), p < 0.001, and 1.16 (1.04-1.30) when ≥ 19 cmH2 O, p = 0.011, a relative risk ratio of 1.18 (1.07-1.30), p = 0.016. Our data support volume-controlled ventilation during surgery, particularly for patients more likely to suffer postoperative pulmonary complications.

Intra-operative protective mechanical ventilation in lung transplantation: a randomised, controlled trial.

Primary graft dysfunction occurs in up to 25% of patients after lung transplantation. Contributing factors include ventilator-induced lung injury, cardiopulmonary bypass, ischaemia-reperfusion injury and excessive fluid administration. We evaluated the feasibility, safety and efficacy of an open-lung protective ventilation strategy aimed at reducing ventilator-induced lung injury. We enrolled adult patients scheduled to undergo bilateral sequential lung transplantation, and randomly assigned them to either a control group (volume-controlled ventilation with 5 cmH2 O, positive end-expiratory pressure, low tidal volumes (two-lung ventilation 6 ml.kg-1 , one-lung ventilation 4 ml.kg-1 )) or an alveolar recruitment group (regular step-wise positive end-expiratory pressure-based alveolar recruitment manoeuvres, pressure-controlled ventilation set at 16 cmH2 O with 10 cmH2 O positive end-expiratory pressure). Ventilation strategies were commenced from reperfusion of the first lung allograft and continued for the duration of surgery. Regular PaO2 /FI O2 ratios were calculated and venous blood samples collected for inflammatory marker evaluation during the procedure and for the first 24 h of intensive care stay. The primary end-point was the PaO2 /FI O2 ratio at 24 h after first lung reperfusion. Thirty adult patients were studied. The primary outcome was not different between groups (mean (SD) PaO2 /FI O2 ratio control group 340 (111) vs. alveolar recruitment group 404 (153); adjusted p = 0.26). Patients in the control group had poorer mean (SD) PaO2 /FI O2 ratios at the end of the surgical procedure and a longer median (IQR [range]) time to tracheal extubation compared with the alveolar recruitment group (308 (144) vs. 402 (154) (p = 0.03) and 18 (10-27 [5-468]) h vs. 15 (11-36 [5-115]) h (p = 0.01), respectively). An open-lung protective ventilation strategy during surgery for lung transplantation is feasible, safe and achieves favourable ventilation parameters.

The effect of pressure-controlled inverse ratio ventilation on lung protection in obese patients undergoing gynecological laparoscopic surgery.

SPECIFIC AIM: To examine the effects of pressure-controlled inverse ratio ventilation (PCIRV) and volume-control ventilation (VCV) on arterial oxygenation, pulmonary function, hemodynamics, levels of surfactant protein A (SP-A), and tumor necrosis factor-α (TNF-α) in obese patients undergoing gynecological laparoscopic surgery. METHODS: Sixty patients, body mass index (BMI) ≥30 kg/m2, scheduled for elective gynecological laparoscopic surgery were enrolled in the study. Patients were randomly allocated to receive either PCIRV with an inspiratory-expiratory (I:E) ratio of 1.5:1 (PCIRV group n = 30) or VCV with an I:E ratio of 1:2 (VCV group n = 30). Ventilation variables, viz. tidal volume (V T), dynamic respiratory-system compliance (C RS), driving pressure (ΔP = V T/C RS), arterial blood oxygen partial pressure/fraction of inspiration oxygen (PaO2/FiO2) and arterial blood carbon dioxide partial pressure (PaCO2), were measured. Hemodynamic variables, viz. mean arterial pressure (MAP), heart rate (HR), and serum levels of SP-A and TNF-α, were also measured. RESULTS: When compared to patients in the VCV group, patients in the PCIRV group had higher V T, dynamic CRS, and PaO2/FiO2, and lower ΔP and PaCO2 at 20 and 60 min after the start of pneumoperitoneum (p < 0.05). Patients in the PCIRV group had lower SP-A and TNF-α levels at 24 and 48 h after surgery than those in the VCV group (p < 0.05). CONCLUSION: In obese patients undergoing gynecological laparoscopic surgery, PCIRV can improve ventilation, promote gas exchange and oxygenation, and is associated with decreased levels of SP-A and TNF-α. These effects demonstrate improved lung protection provided by PCIRV in this patient population.

Effects of pulmonary artery perfusion with urinary trypsin inhibitor as a lung protective strategy under hypothermic low-flow cardiopulmonary bypass in an infant piglet model.

OBJECTIVE: This study aimed to evaluate the effects of pulmonary artery perfusion with a urinary trypsin inhibitor (UTI) as a lung protective strategy in order to provide an experimental basis for immature lung clinical protective strategies on deep hypothermia with low-flow (DHLF) cardiopulmonary bypass (CPB)-induced pulmonary injury in an infant piglet model. METHODS: The piglets (n=15), aged 18.7±0.3 days, weight 4.48±0.21kg, were randomly divided into 3 groups, with 5 piglets in each group: the control group, the pulmonary artery perfusion without UTI group (Group P) and the pulmonary artery perfusion with UTI group (Group U). The levels of the cytokines tumour necrosis factor-α, myeloperoxidase, malondialdehyde and interleukin-10 (TNF-α, MPO, MDA and IL-10) in pulmonary venous serum and lung tissue and the activity of NF-kappa B in lung tissue were measured by enzyme-linked immunosorbent assay (ELISA) and electrophoresis mobility shift assay (EMSA), respectively. RESULTS: After DHLF-CPB, all of the piglets demonstrated a state of lung injury as a deterioration of lung function indices, lung injury scores, pulmonary ultrastructure changes, expression of TNF-α, MPO, MDA and IL-10 and the activities of nuclear factor-kappa B (NF-κB), while pulmonary artery perfusion with UTI significantly ameliorated lung function and histopathological changes, with greatly decreased serum levels of TNF-α and MPO compared to the other two groups. Also, we found an increase in the level of IL-10 in Group U lungs compared with that in Group P lungs, which correlated with a strong inhibition in the activity of NF-κB. CONCLUSION: Pulmonary artery perfusion with UTI ameliorated the DHLF-induced immature pulmonary injury in the lungs via a reduction of pro-inflammatory cytokine expression and up-regulated levels of IL-10 by inhibiting the activity of NF-κB.

Effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery.

OBJECTIVE: This research aimed to ascertain the effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery. METHODS: Obese patients undergoing laparoscopic surgery under general anesthesia were separated into the control group (group C) and the dexmedetomidine group (group D) (n = 30). Patients in group D were infused with dexmedetomidine (1 µg/kg) intravenously for 10 min and then at a rate of 0.5 mg/kg h until 30 min before the end of the surgery, and those in group C were infused with an equal volume of saline. The surgery time points were divided into: before anesthesia induction (T0), 5 min after intubation (T1), 30 min after pneumoperitoneum (T2), 10 min after pneumoperitoneum release (T3), at the time of extubation (T4), 3 min after extubation (T5), and 24 h after surgery (T6). Arterial blood was collected for blood gas analysis to record arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). Dynamic lung compliance (Cdyn), oxygenation index (OI), alveolar-arterial oxygen partial pressure difference (A-aDO2), and respiratory index (RI) were calculated. The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation were recorded. Plasma IL-8 and IL-10 levels were measured from T0 to T6. RESULTS: The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation in group D were not statistically significant when compared with those in group C. Versus at the T1 time point, A-aDO2 and RI were higher and Cdyn and OI were lower in both groups at T2 and T3 time points. Versus group C, group D had higher Cdyn and OI and lower A-aDO2 and RI at T2 and T3 time points. Versus at the T0 time point, at each time point from T1 to T6, IL-8 and IL-10 levels were higher in both groups. Versus group C, group D had lower IL-8 and higher IL-10 levels at each time point from T1 to T6. CONCLUSION: In obese patients undergoing laparoscopic surgery under general anesthesia, the use of dexmedetomidine can improve the lung compliance and OI of the patients, inhibit the inflammatory response of the lungs of the patients and thus have a certain protective effect on the lung function.

Effect of ultrasound-guided stellate ganglion block on lung protection for patients undergoing one-lung ventilation.

OBJECTIVE: To explore the potential effect of ultrasound-guided stellate ganglion block (SGB) on lung protection for patients undergoing one-lung ventilation (OLV). METHODS: A total of 123 patients undergoing elective one-lung ventilation surgery were selected as research subjects in this prospective study. These patients were randomly divided into the SGB group, control group and blank group on average. Stellate ganglion block was carried out in the SGB and control groups. Patients in the SGB group were injected with 6 ml mixture of 0.25% ropivacaine hydrochloride and 1% lidocaine hydrochloride, while those in the control group were injected with 6 mL of 0.9% saline. Punctures weren't performed for patients in the blank group. The same induction and maintenance of general anesthesia was adopted for all three groups. Hemodynamics, respiratory parameters and arterial blood gas analysis were recorded after entering the operation room (T0), pre-OLV (T1), 30 min after OLV (T2), 60 min after OLV (T3), at the end of surgery (T4), and 30 min after extubation (T5). Oxygenation index (OI), pulmonary shunt fraction (Qs/Qt) and pH value were compared at different time points. Intravenous serum was collected at T0, T3 and T5 for the detection of surfactant proteins A (SP-A), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6) and interleukin-10 (IL-10) levels, respectively. The complications related to SGB after surgery and the postoperative pulmonary complications within 72 h were recorded. RESULTS: At T1, T2, and T3, MAP level in SGB group was lower than that in blank and control groups (P<0.05). At T2, and T3, SGB group had lower hear rate (HR), peak airway pressure (Ppeak) and tidal volume (TV) than blank and control groups (all P<0.05). From T2 to T5, SGB group had higher OI but lower Qs/Qt than blank and control groups (both P<0.05). At T3 and T5, SGB group had lower SP-A, IL-6, and MDA levels but higher IL-10 and SOD levels than blank and control groups (all P<0.05). There was one case of hypoxemia in the blank group within 72 h after surgery. CONCLUSION: Ultrasound-guided SGB has lung-protective effects on patients undergoing OLV, which significantly improves patients' OI, reduces intrapulmonary shunts, declines ventilator-induced lung damage, and inhibits inflammatory response as well as oxidative stress (China Clinical Trial Registry, registration number ChiCTR2000033385, https://www.chictr.org.cn).

Low Frequency Ventilation During Cardiopulmonary Bypass to Protect Postoperative Lung Function in Cardiac Valvular Surgery: The PROTECTION Phase II Randomized Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) triggers pulmonary injury. In this trial we assessed the feasibility, safety, and efficacy of low frequency ventilation (LFV) during CPB in patients undergoing valvular surgery. METHODS AND RESULTS: Patients with severe mitral or aortic valve disease were randomized to either LFV or usual care. Primary outcomes included release of generic inflammatory and vascular biomarkers and the lung-specific biomarker sRAGE (soluble receptor for advance glycation end products) up to 24 hours postsurgery. Secondary outcomes included pulmonary function tests and 6-minute walking test up to 8 weeks postdischarge. Sixty-three patients were randomized (33 LFV versus 30 usual care). Mean age was 66.8 years and 30% were female. LFV was associated with changes of sRAGE (soluble receptor for advance glycation end products) levels (geometric mean ratio, 3.05; [95% CI, 1.13-8.24] 10 minutes post CPB, and 1.07 [95% CI, 0.64-1.79], 0.84 [95% CI, 0.55-1.27], 0.67 [95% CI, 0.42-1.07], and 0.62 [95% CI, 0.45-0.85] at 2, 6, 12, and 24 hours post CPB respectively). No changes were observed for any of the generic biomarkers. Respiratory index soon after surgery (mean difference, -0.61 [95% CI, -1.24 to 0.015] 10 minutes post end of CPB), forced expiratory volume after 1 second/forced vital capacity ratio (0.050 [95% CI, 0.007-0.093] at 6 to 8 weeks pos-surgery), Forced vital capacity alone (95% CI, -0.191 L [-0.394 to 0.012]) and 6-minute walking test score at discharge (63.2 m [95% CI, 12.9-113.6]) were better preserved in the LFV group. No other differences were noted. CONCLUSIONS: The use of LFV during CPB in patients undergoing valvular surgery was feasible and safe and was associated with changes in sRAGE levels along with better preserved lung function and walking performance. These observations warrant further investigation in larger future studies. REGISTRATION: URL: https://www.isrctn.com; Unique Identifier: ISRCTN75795633.

Identification of anti-fibrotic and pro-apoptotic bioactive compounds from Ganoderma formosanum and their possible mechanisms in modulating TGF-ß1-induced lung fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties. AIM OF THE STUDY: The aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy. METHODS AND MATERIALS: G. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-ß1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations. RESULTS: The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-ß1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-ß receptor 1. CONCLUSION: Potential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts.