Association of mechanical power during one-lung ventilation and post-operative pulmonary complications among patients undergoing lobectomy: a protocol for a prospective cohort study.

The association of intra-operative mechanical power (MP) with post-operative pulmonary complications (PPCs) has been described before, but it is uncertain whether the potential inherent bias can limit the use of this parameter, particularly in the context of one-lung ventilation. This single-center study aims to investigate the effect of MP during one-lung ventilation (OLV), and the risks of PPCs in patients undergoing thoracoscopic lobectomy. This prospective observational study is being conducted in an academic tertiary hospital in mainland China. Participants diagnosed with lung cancer, and aged 50 to 80 years are eligible. Video-assisted thoracoscopic surgery (VATS) lobectomy is performed for all patients. The primary outcome is the occurrence of PPCs over 5 consecutive days after the surgery, or until discharge from the hospital. Secondary outcomes include the composite conditions of PPCs, in-hospital stay, systematic inflammation tested by blood samples, and changes in aeration compartments in the ventilated lung as assessed by CT scans. We aim to evaluate the association of mean MP and the temporal patterns in the trend of MP during OLV with the occurrence of PPCs. A total of 120 patients will be enrolled in this study. The study protocol has received approval from the Ethics Committee of the affiliated hospital of Southwest Medical University, China (Reference number: KY2022162). The findings will be made available to the funder and researchers via scientific conferences and peer-reviewed publications. This controlled trial was approved by the Ethics Committee of Southwest Medical University(ChiCTR2200062173), and registered in the Chinese Clinical Trial Register website ( http://www.chictr.org.cn/edit.aspx?pid=172533&htm=4 , ChiCTR2200062173). A written consent was obtained from each patient.

Melatonin alleviates intestinal injury, neuroinflammation and cognitive dysfunction caused by intestinal ischemia/reperfusion.

Intestinal ischemia/reperfusion (I/R) can cause multiple organ damage with extremely high morbidity and mortality. Melatonin has anti-inflammatory, anti-oxidative and anti-apoptotic effects against various diseases. This study aimed to explore whether melatonin had a protective effect against intestinal I/R-induced neuroinflammation and cognitive dysfunction, and investigate its potential mechanisms. In this study, melatonin was administered to the rats with intestinal I/R, then histological changes in intestine and brain (frontal cortex and hippocampal CA1 area) tissues and cognitive function were detected, respectively. The encephaledema and blood-brain barrier (BBB) permeability were observed. Moreover, the alterations of proinflammatory factors (tumor necrosis factor-α, interleukin-6 and interleukin-1ß), oxidative response (malondialdehyde, superoxide dismutase, and reactive oxygen species), apoptosis and proteins associated with inflammation,including Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and phosphorylated nuclear factor kappa beta (NF-κB), and apoptosis (cleaved caspase-3) in brain tissues were examined. Furthermore, the expressions of TLR4, Myd88, and microglial activity were observed by multiple immunofluorescence staining. The results showed that intestinal I/R-induced abnormal neurobehavior and cerebral damage were ameliorated after melatonin treatment, which were demonstrated by improved cognitive dysfunction and aggravated histology. Furthermore, melatonin decreased the levels of proinflammatory factors and oxidative stress in plasma, intestine and brain tissues, attenuated apoptotic cell, and inhibited the expressions of related proteins and the immunoreactivity of TLR4 or Myd88 in microglia in brain tissues. These findings showed that melatonin might relieve neuroinflammation and cognitive dysfunction caused by intestinal I/R, which could be, at least partially, related to the inhibition of the TLR4/Myd88 signaling in microglia.

MicroRNA-140 inhibits skeletal muscle glycolysis and atrophy in endotoxin-induced sepsis in mice via the WNT signaling pathway.

Sepsis is a systemic inflammatory response syndrome resulting from infection. This study aimed at exploring the role of microRNA-140 (miR-140) in septic mice. Wnt family member 11 (WNT11) was verified to be a target gene of miR-140 after bioinformatic prediction and dual luciferase reporter gene assay. Importantly, miR-140 negatively regulated WNT11. We initially induced the model of sepsis by endotoxin, and then ectopic expression and knockdown experiments were performed to explore the functional role of miR-140 in sepsis. Additionally, cross-sectional areas of muscle fiber, lactic acid production, 3-methylhistidine (3-MH) and tyrosine (Tyr) production in extensor digitorium longus (EDL) muscles, and serum levels of inflammatory factors were examined. The effect of miR-140 on the expression of WNT signaling pathway-related and apoptosis-related factors in skeletal muscle tissue was determined. The experimental results indicated that upregulated miR-140 or silenced WNT11 increased cross-sectional areas of muscle fiber while decreasing lactic acid production, skeletal muscle cell apoptosis [corresponding to downregulated B cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3 and upregulated Bcl-2], and the proteolytic rate of Tyr and 3-MH. Also, overexpressed miR-140 or silenced WNT11 reduced inflammation as reflected by decreased serum levels of IL-6, IL-10, and TNF-α. Furthermore, overexpression of miR-140 was shown to suppress the activation of the WNT signaling pathway, accompanied by decreased expression of WNT11, ß-catenin, and GSK-3ß. Taken together, upregulation of miR-140 could potentially inhibit skeletal muscle lactate release, an indirect measure of glycolysis, and atrophy in septic mice through suppressing the WNT signaling pathway via inhibiting WNT11 expression.

RNase attenuates acute lung injury induced by ischemia-reperfusion in mice.

Treatment with ribonuclease (RNase) reportedly protects the heart after myocardial ischemia-reperfusion (I/R), but its potential effect on lung I/R injury (LIRI) is unknown. Thus, we aim to explore whether RNase treatment would relieve LIRI. Thirty-six C57BL/6J adult male wild-type mice were evenly divided into I/R+RNase (I/R+R) group, I/R group, and sham group. Lung I/R was induced by left pulmonary hilum occlusion for 1h and reperfusion for 2h. All mice were treated with RNase or same dosage of normal saline in advance. After I/R, blood and lung tissues were collected for analysis. The results showed that lung injury scores, wet/dry ratio, expressions of inflammatory cytokines, pulmonary apoptosis, and levels of serum extracellular RNA (exRNA), including microRNAs, were markedly elevated after I/R. However, RNase treatment significantly attenuated cytokine production in both lung tissue and serum and also suppressed pulmonary apoptosis as reflected by TUNEL staining and activated caspase-3. In addition, total serum exRNA levels in the I/R+R group had a downward trend versus the I/R group. In conclusion, the increase of circulating exRNA levels contributed to LIRI in adult mice, which could be relieved by injection of RNase during perioperative window. The potential mechanism is the decrease of serum exRNA level and the suppression of pulmonary inflammation and apoptosis.

Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and puncture.

BACKGROUND: Sepsis is associated with high morbidity and mortality, and survivors can present with cognitive dysfunction. The present study was performed to investigate the effects of hydrogen-rich saline (HRS) on oxidative stress in the brain, cognitive dysfunction, and mortality in a rat model of sepsis. METHODS: A rat model of sepsis was induced by cecal ligation and puncture. Physiologic saline or HRS was administered intraperitoneally (2.5 mL/kg or 10 mL/kg) 10 min before the operation. The survival rate was recorded, and cognitive function was tested using the Morris water maze. The reactive oxygen species and malondialdehyde levels and superoxide dismutase activity in the hippocampus were observed to evaluate the oxidative stress levels. The caspase 3 levels were measured to detect apoptosis. The histopathologic changes in the hippocampus were evaluated by hematoxylin-eosin staining and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. RESULTS: Cecal ligation and puncture resulted in a poor survival rate, evidence of brain injury, and cognitive dysfunction. The hippocampal reactive oxygen species and malondialdehyde levels increased significantly, and superoxide dismutase activity decreased significantly. HRS reversed these changes in a dose-dependent manner. CONCLUSIONS: These findings indicate that HRS could attenuate the consequences of sepsis induced by cecal ligation and puncture in rats, at least in part, by the inhibition of oxidative stress.