Lung ischemia‐reperfusion (IR) injury is a common clinical pathology associated with high mortality. Ferroptosis, a novel mode of cell death elicited by iron‐dependent phospholipid peroxidation, has been implicated in ischemic events. Acyl‐CoA synthetase long‐chain family member 4 (ACSL4) is one of the main enzymes in pro‐ferroptotic lipid metabolism. In this study, the involvement of ferroptotic death in different durations of reperfusion was evaluated by assessing the iron content, malondialdehyde, and glutathione levels, ferroptosis‐related protein expression, and mitochondria morphology. The roles of ferroptosis‐specific inhibitor, liproxastin‐1 (Lip‐1), and ACSL4 modulation in a preventive regimen were assessed in vivo and in vitro. The hallmarks of pulmonary function, such as histological lung injury score, wet/dry ratio, and oxygenation index, were evaluated as well. Results showed that lung IR increased the tissue iron content and lipid peroxidation accumulation, along with key protein (GPX4 and ACSL4) expression alteration during reperfusion. Pretreatment with Lip‐1 inhibited ferroptosis and ameliorated lung IR‐induced injury in animal and cell models. In addition, administering ACSL4 inhibitor rosiglitazone before ischemia diminished the ferroptotic damage in IR‐injured lung tissue, consistent with the protective effect of ACSL4 knockdown on lung epithelial cells subjected to hypoxia/reoxygenation. Thus, this study delineated that IR‐induced ferroptotic cell death in lung tissue and ACSL4 were correlated with this process. Inhibition of ferroptosis and ACSL4 mitigated the ferroptotic damage in IR‐induced lung injury by reducing lipid peroxidation and increasing the glutathione and GPX4 levels.

Ferroptosis is a unique and pervasive form of regulated cell death driven by iron-dependent phospholipid peroxidation. It results from disturbed cellular metabolism and imbalanced redox homeostasis and is regulated by various cellular metabolic pathways. Recent preclinical studies have revealed that ferroptosis may be an attractive therapeutic target in fibrotic diseases, such as liver fibrosis, pulmonary fibrosis, kidney fibrosis, and myocardial fibrosis. This review summarizes the latest knowledge on the regulatory mechanism of ferroptosis and its roles in fibrotic diseases. These updates may provide a novel perspective for the treatment of fibrotic diseases as well as future research.

Importance. Postoperative cognitive dysfunction (POCD) occurs in 6%–53% of elderly patients receiving major surgery and is related to longer hospital stays, increased hospital costs, and 1‐year mortality. An increasing number of studies suggest that using dexmedetomidine (Dex) in critical care units is associated with reduced incidence of delirium. However, perioperative use of Dex for the prevention of POCD has not been well studied. Objective. To evaluate whether a low‐dose perioperative infusion of Dex reduces early POCD. Design. This study was a double‐blind, randomized, placebo‐controlled trial that randomly assigned patients to Dex or saline placebo infused during surgery and patient‐controlled intravenous analgesia (PCIA) infusion. Patients were assessed for postoperative cognitive decline. Interventions. Dex was infused at a loading dose of 0.5 μg/kg intravenously (15 min after entering the operation room) followed by a continuous infusion at a rate of 0.5 μg/kg/h until one‐lung ventilation or artificial pneumothorax ended. Patients in the Dex group received regular PCIA pump with additional dose of Dex (200 μg). Results. In total, 126 patients were randomized, and 102 patients were involved in the result analysis. The incidence of POCD was 36.54% (19/52) in the Dex group and 32.00% (16/50) in the normal saline (NS) group, with no statistic difference. No significant difference was observed between the two groups in terms of Telephone Interview for Cognitive Status‐Modified (TICS‐m) scores at different times. However, the TICS‐m score at 7 days after surgery was significantly lower than that at 30 days in 102 patients (32.93 ± 0.42 vs. 33.92 ± 0.47, P = 0.03). The visual analogue scale scores in the Dex group were significantly lower than those in the NS group 1 day postoperation at rest and activity (2.00 [1.00–3.00] vs. 3.00 [2.00–4.00], P < 0.01; 4.00 [3.00–5.00] vs. 5.00 [4.00–6.00], P < 0.05, respectively). Patients receiving Dex or NS had no statistical difference in activities of daily living (ADLs) scores at 7 and 30 days after surgery, but the ADL score at 30 days after surgery showed a significant reduction compared with that at 7 days (P < 0.01). Patients in the Dex group had a shorter hospital length of stay (15.26 ± 3.77 vs. 17.69 ± 5.09, P = 0.02) and less expenses (52458.71 ± 10649.30 vs. 57269.03 ± 9269.98, P = 0.04) than those in the NS group. Conclusions. Low‐dose Dex in the perioperative period did not reduce the incidence of early POCD in thoracic surgery. However, it relieved postoperative pain, decreased the hospitalization expenses, and shortened the length of stay.

BACKGROUND:Atelectasis occurs in patients of all ages during various surgeries. Previous studies have mainly focused on perioperative atelectasis in infants. However, research on the incidence of atelectasis among elderly patients, particularly those undergoing laparoscopic surgeries, is limited. Therefore, this prospective study aimed to investigate the effect of lung recruitment maneuvers (LRMs) on the reduction of atelectasis determined by lung ultrasound in patients more than 60 years old undergoing laparoscopic surgery for colorectal carcinoma. MATERIAL AND METHODS:In this evaluator-blinded clinical study, 42 patients more than 60 years old diagnosed with colorectal carcinoma were randomly grouped either into a lung recruitment maneuver (RM) group or control (C) group. All patients were scheduled for laparoscopic surgery under general anesthesia using the lung-protective ventilation strategy. Lung ultrasonography was carried out at 3 predetermined time intervals. Patients in the RM group received ultrasound-guided recruitment maneuvers once atelectasis was discovered by lung ultrasound. Scores of lung ultrasound were used for assessing the severity of lung atelectasis. RESULTS:At the end of the operation, the occurrence of atelectasis was 100% in the RM group and 95% in the C group. After RMs, the frequency of atelectasis in the RM group and C group was 50% and 95%, respectively (P<0.01). Postoperative pulmonary complications were not different between the 2 groups. CONCLUSIONS:At a single center, patients more than 60 years old undergoing laparoscopic surgery for colorectal carcinoma had a prevalence of lung atelectasis of 100% and although LRMs significantly reduced the incidence of pulmonary atelectasis, they did not improve postoperative pulmonary complications.

Pulmonary fibrosis is a chronic progressive form of interstitial lung disease, characterized by the histopathological pattern of usual interstitial pneumonia. Apart from aberrant alterations of protein-coding genes, dysregulation of non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs (circRNAs), is crucial to the initiation and progression of pulmonary fibrosis. CircRNAs are single-stranded RNAs that form covalently closed loops without 5′ caps and 3′ tails. Different from canonical splicing of mRNA, they are produced from the back-splicing of precursor mRNAs and have unique biological functions, as well as potential biomedical implications. They function as important gene regulators through multiple actions, including sponging microRNAs and proteins, regulating transcription, and splicing, as well as protein-coding and translation in a cap-independent manner. This review comprehensively summarizes the alteration and functional role of circRNAs in pulmonary fibrosis, with a focus on the involvement of the circRNA in the context of cell-specific pathophysiology. In addition, we discuss the diagnostic and therapeutic potential of targeting circRNA and their regulatory pathway mediators, which may facilitate the translation of recent advances from bench to bedside in the future.