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Abstract Background For patients receiving one lung ventilation in thoracic surgery, numerous studies have proved the superiority of lung protective ventilation of low tidal volume combined with recruitment maneuvers (RM) and individualized PEEP. However, RM may lead to overinflation which aggravates lung injury and intrapulmonary shunt. According to CT results, atelectasis usually forms in gravity dependent lung regions, regardless of body position. So, during anesthesia induction in supine position, atelectasis usually forms in the dorsal parts of lungs, however, when patients are turned into lateral decubitus position, collapsed lung tissue in the dorsal parts would reexpand, while atelectasis would slowly reappear in the lower flank of the lung. We hypothesize that applying sufficient PEEP without RM before the formation of atelectasis in the lower flank of the lung may beas effective to prevent atelectasis and thus improve oxygenation as applying PEEP with RM. Methods A total of 84 patients scheduled for elective pulmonary lobe resection necessitating one lung ventilation will be recruited and randomized totwo parallel groups. For all patients, one lung ventilation is initiated the right after patients are turned into lateral decubitus position. For patients in the study group, individualized PEEP titration is started the moment one lung ventilation is started, while patients in the control group will receive a recruitment maneuver followed by individualized PEEP titration after initiation of one lung ventilation. The primary endpoint will be oxygenation index measured at T4. Secondary endpoints will include intrapulmonary shunt, respiratory mechanics, PPCs, and hemodynamic indicators. Discussion Numerous previous studies compared the effects of individualized PEEP applied alone with that applied in combination with RM on oxygenation index, PPCs, intrapulmonary shunt and respiratory mechanics after atelectasis was formed in patients receiving one lung ventilation during thoracoscopic surgery. In this study, we will apply individualized PEEP before the formation of atelectasis while not performing RM in patients allocated to the study group, and then we’re going to observe its effects on the aspects mentioned above. The results of this trial will provide a ventilation strategy that may be conductive to improving intraoperative oxygenation and avoiding the detrimental effects of RM for patients receiving one lung ventilation. Trial registration www.Chictr.org.cn ChiCTR2400080682. Registered on February 5, 2024.

Abstract Background N6-methyladenosine (m6A) methylation is the most abundant chemical posttranscriptional modification of mRNA, and it is associated with the regulation of the immune response to tumors. However, the function of m6A modification in the immune response to endometrial cancer (EC) remains unknown. Our study investigated the immunological role of methyltransferase-like 3 (METTL3) in EC and the underlying molecular mechanism. Methods We investigated the correlation between the expression of METTL3 and CD8 by using an endometrial tissue microarray cohort. Next, we investigated the role and mechanism of METTL3 in the immune response to EC using a mouse tumor model and a CD8+ T cell-EC cell coculture system after METTL3 overexpression or depletion. Additionally, RNA immunoprecipitation (RIP), methylated RIP, and RNA stability experiments were used to investigate the mechanism underlying the function of METTL3 in immunosurveillance of EC. Results METTL3 levels were downregulated in EC patients, low levels of METTL3 were correlated with poor prognosis in EC patients. There was a positive correlation between METTL3 expression and CD8 expression. Overexpression of METTL3 in the EC cell and CD8+ T cell coculture system inhibited EC cell proliferation, migration, and promoted CD8+ T-cell proliferation, and in vivo, METTL3 overexpression increased CD8+ T cell proportions and inhibited EC progression; however, genetic depletion of METTL3 exerted the opposite effects. NLR family CARD domain-containing 5 (NLRC5) was identified as a target of METTL3-mediated m6A modification. The degradation of NLRC5 was increased by YTH domain-containing family 2 (YTHDF2). Conclusions Overall, METTL3, YTHDF2, and NLRC5 have potential to be the diagnostic and prognostic biomarkers for EC. METTL3 facilitated the m6A modifications of NLRC5 and inhibited its degradation through a YTHDF2-dependent mechanism in EC. Genetic overexpression of METTL3 attenuated the immune evasion of EC by promoting NLRC5-mediated immunosurveillance, suggesting that the METTL3/YTHDF2/NLRC5 axis is a promising target of immunotherapy in EC.

Abstract Background The incidence of postoperative pulmonary complications (PPCs) is higher in obese patients undergoing general anesthesia and mechanical ventilation due to the reduction of oxygen reserve, functional residual capacity, and lung compliance. Individualized positive end-expiratory pressure (iPEEP) along with other lung-protective strategies is effective in alleviating postoperative atelectasis. Here, we compared the best static lung compliance (Cstat) titration of iPEEP with electrical impedance tomography (EIT) titration to observe their effects on postoperative atelectasis in obese patients undergoing laparoscopic surgery. Methods A total number of 140 obese patients with BMI ≥ 32.5kg/m2 undergoing elective laparoscopic gastric volume reduction and at moderate to high risk of developing PPCs will be enrolled and randomized into the optimal static lung compliance-directed iPEEP group and EIT titration iPEEP group. The primary endpoint will be pulmonary atelectasis measured and calculated by EIT immediately after extubation and 2 h after surgery. Secondary endpoints will be intraoperative oxygenation index, organ dysfunction, incidence of PPCs, hospital expenses, and length of hospital stay. Discussion Many iPEEP titration methods effective for normal weight patients may not be appropriate for obese patients. Although EIT-guided iPEEP titration is effective in obese patients, its high price and complexity limit its application in many clinical facilities. This trial will test the efficacy of iPEEP via the optimal static lung compliance-guided titration procedure by comparing it with EIT-guided PEEP titration. The results of this trial will provide a feasible and convenient method for anesthesiologists to set individualized PEEP for obese patients during laparoscopic surgery. Trial registration ClinicalTrials.gov ChiCTR2000039144 . Registered on October 19, 2020