Elk1 enhances inflammatory cell infiltration and exacerbates acute lung injury/acute respiratory distress syndrome by suppressing Fcgr2b transcription.

OBJECTIVE: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with significant mortality rates. The role of Fcgr2b in the pathogenesis of ALI/ARDS is not fully elucidated. This study aimed to investigate the functions of Fcgr2b in ALI/ARDS and explore its underlying mechanisms. METHODS: Methods: In this study, rat models of ARDS and pulmonary microvascular endothelial cell (PMVEC) injury models were established through the administration of lipopolysaccharide (LPS). The expression levels of Fcgr2b and Elk1 were quantified in both LPS-induced ARDS rats and PMVECs. Subsequent gain- and loss-of-function experiments were conducted, followed by comprehensive assessments of lung tissue for pathomorphological changes, edema, glycogen storage, fibrosis, and infiltration of inflammatory cells. Additionally, bronchoalveolar lavage fluid was analyzed for T-helper 17 (Th17) cell infiltration, inflammatory response, and microvascular permeability to evaluate lung injury severity in ARDS models. Furthermore, the activity, cytotoxicity, apoptosis, and angiogenic potential of PMVECs were assessed to gauge cell injury. The interaction between Elk1 and Fcgr2b was also examined to confirm their regulatory relationship. RESULTS: In the context of LPS-induced ARDS and PMVEC injury, Fcgr2b expression was markedly reduced, whereas Elk1 expression was elevated. Overexpression of Fcgr2b led to a decrease in Th17 cell infiltration and mitigated lung tissue damage in ARDS models, in addition to reducing LPS-induced injury in PMVECs. Elk1 was found to suppress Fcgr2b transcription through the recruitment of histone 3 lysine 9 trimethylation (H3K9me3). Knockdown of Elk1 diminished Th17 cell infiltration and lung tissue damage in ARDS models, and alleviated LPS-induced injury in PMVECs, effects that were reversed upon Fcgr2b upregulation. CONCLUSION: Elk1 negatively regulates Fcgr2b transcription, thereby augmenting the inflammatory response and exacerbating lung injury in LPS-induced ALI/ARDS.

Airway Management of the Right Anterior Segmentectomy through Uniportal video-assisted thoracoscopic surgery (VATS) after left pneumonectomy by an adapted double-lumen endobronchial tube (DLT): a case report.

BACKGROUND: Lung resection after previous contralateral pneumonectomy is rare. We present a case of right anterior segmentectomy despite previous left pneumonectomy, demanding special airway management strategy. CASE PRESENTATION: A 48-year-old woman who had left pneumonectomy 2 years ago was scheduled to have the right anterior segmentectomy through uniportal video-assisted thoracoscopy (VATS). A 32-French (Fr) left-sided double-lumen endobronchial tube (DLT) was chosen and adapted. The DLT was intubated into the bronchus intermedius. And the upper lobe can be isolated from the ventilation in the middle and lower lobes when the bronchial cuff's inflated. The perioperative period was uneventful and the pathological diagnosis was adenocarcinoma. CONCLUSION: Lung cancer radical resection was discouraged after previous contralateral pneumonectomy partly due to the challenging ventilation and isolation. With this new DLT adapting and intubation technique showed in this case, the challenging ventilation and isolation that deter the implementation of the operation mentioned above could be solved.

The Influence of Piriform Recess Instillation with Lidocaine Before Bronchoscopy on Post-General Anesthesia Cough: A Randomized Controlled Trial.

Background and Importance: Postoperative cough is a common complication of general anesthesia after bronchoscopy. The aim of the present study was to determine the safety profile and efficacy of piriform recess instillation with lidocaine in reducing the incidence of coughing. Objective: To what extent could piriform recess instillation with lidocaine decrease the incidence of cough at 10min after extubation? Outcome Measures and Analysis: Eighty-eight consecutive patients were equally randomized to a lidocaine group receiving piriform recess instillation with 2mL 2% lidocaine, and a normal saline group receiving piriform recess instillation with 2mL saline. The primary outcome was the incidence of cough after extubation, and the secondary outcomes were throat score at 10 min and 6 h after extubation assessed by the numerical rating scale, cough severity at 10 min and 6 h after extubation assessed by the Visual Analog Scale (VAS), 24 h 40-item Quality of Recovery Score (QoR-40), and subject-rated satisfaction score on a VAS. Main Results: Compared with saline group, the incidence of cough in lidocaine group was significantly lower (63.6% vs 86.4%, P=0.014). The sore throat score at 10 min after extubation was significantly lower (0[0,0] vs 1[0,2], P<0.001). The subject-rated overall anesthesia satisfaction score was significantly higher (84.8[±6.2] vs 76.6[±8.6], P<0.001). The severity of cough at 10 min after extubation was significantly lower (Mild: 36.4% vs 11.4%, P=0.006; Severe: 9.1% vs 43.2%, P<0.001). There was no significant difference in the sore throat score at 6 h after extubation, severity of cough at 6 h after extubation, or QoR-40 at 24 h after extubation between the two groups. Conclusion: Piriform recess instillation with lidocaine before bronchoscopy is a simple and effective method for reducing early cough intensity and alleviating early sore throat. At 6 hours, there were no differences observed between the groups. Clinical Trial Registration: Chinese Clinical Trial Registry (identifier: ChiCTR2200067087).

Supraglottic jet oxygenation and ventilation via nasopharyngeal airway for a patient with iatrogenic tracheoesophageal fistula: A case report.

Background: Iatrogenic tracheoesophageal fistula (TEF) is a rare but life-threatening condition. No consensus has been reached regarding TEF treatment, though, stenting has been gaining popularity for less invasiveness than thoracic surgery. The airway management during stent placement for TEF could be challenging. Case presentations: We report a patient who suffered from TEF after cardiac surgery with symptoms of persistent coughing and aspiration. He who was admitted for stent placement but ended up in failure and referred to our institution for further treatment. We successfully took advantage of the supraglottic jet oxygenation and ventilation (SJOV) during stent placement. Conclusion: This is the first case so far describing SJOV in complicated stenting treatment. This demonstrates that SJOV can be applied for stent placement in TEF patients with restricted airways.

CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells, pulmonary microvascular endothelial cells, and pericytes under hypoxia.

BACKGROUND: Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. METHODS: Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real-time polymerase chain reaction, Cell Counting Kit-8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. RESULTS: PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA-432-5p (miR-432-5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR-433-3p in PMECs, and upregulate zinc finger AN1-type containing 5 (ZFAND5) expression by targeting miR-3613-5p in PCs. CONCLUSIONS: Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs, through the miR-433-3p/MXI1 axis in PMECs, and through the miR-3613-5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.

Biology and function of pericytes in the vascular microcirculation.

Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines, thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation. Moreover, due to the characteristics of stem cells, pericytes can differentiate into a variety of inflammatory cell phenotypes, which then affect the immune function. Additionally, pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders. Here we review the origin, biological phenotype and function of pericytes, and discuss the potential mechanisms of pericytes in vascular microcirculation disorders, especially in pulmonary hypertension, so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.

MiR-122-5p as a potential regulator of pulmonary vascular wall cell in idiopathic pulmonary arterial hypertension.

MicroRNAs (miRNAs) are versatile regulators of pulmonary arterial remodeling in idiopathic pulmonary arterial hypertension (IPAH). We herein aimed to characterize miRNAs in peripheral blood mononuclear cell (PBMC) and plasma exosomes, and investigate specific miRNA expression in pulmonary artery cells and lung tissues in IPAH. A co-dysregulated miRNA was identified from the miRNA expression profiles of PBMC and plasma exosomes in IPAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the potential function of differentially expressed miRNAs. Real-time quantitative reverse transcription polymerase chain reaction was used to validate the expression of specific miRNAs in hypoxia-induced pulmonary microvascular endothelial cells (PMECs), pulmonary artery smooth muscle cells (PASMCs), pericyte cells (PCs), and lung tissues of patients with IPAH and rats. Finally, the miRNA-mRNA mechanisms of miR-122-5p were predicted. MiR-122-5p was the only co-upregulated miRNA in PBMC and plasma exosomes in patients with IPAH. Functional analysis of differentially expressed miRNAs revealed associations with the GO terms "transcription, DNA-templated," "cytoplasm," and "metal ion binding" in both PBMC and plasma exosomes, KEGG pathway MAPK signaling in PBMC, and KEGG-pathway human papillomavirus infection in plasma exosomes. Hypoxic PMECs and PCs, lung tissue of patients with IPAH, and rats showed increased expression of miR-122-5p, but hypoxic PASMCs showed decreased expression. And miR-122-5p mimics and inhibitor affected cell proliferation. Finally, miR-122-5p was found to potentially target DLAT (in lung tissue) and RIMS1 (in PMECs) in IPAH. According to the dual-luciferase assay, miR-122-5p bound to DLAT or RIMS1. In studies, DLAT imbalance was associated with cell proliferation and migration, RIMS1 is differentially expressed in cancer and correlated with cancer prognosis. Our findings suggest that the miR-122-5p is involved in various biological functions in the adjacent vascular wall cells in IPAH.

Extracorporeal membrane oxygenation support for lung transplantation: Initial experience in a single center in China and a literature review.

Background: Extracorporeal membrane oxygenation (ECMO) is a versatile tool associated with favorable outcomes in the field of lung transplantation (LTx). Here, the clinical outcomes and complications of patients who underwent LTx with ECMO support, mainly prophylactically both intraoperatively and post-operatively, in a single center in China are reviewed. Methods: The study cohort included all consecutive patients who underwent LTx between January 2020 and January 2022. Demographics and LTx data were retrospectively reviewed. Perioperative results, including complications and survival outcomes, were assessed. Results: Of 86 patients included in the study, 32 received ECMO support, including 21 who received prophylactic intraoperative use of ECMO with or without prolonged post-operative use (pro-ECMO group), while the remaining 54 (62.8%) received no external support (non-ECMO group). There were no significant differences in the incidence of grade 3 primary graft dysfunction (PGD), short-term survival, or perioperative outcomes and complications between the non-ECMO and pro-ECMO groups. However, the estimated 1- and 2-year survival were superior in the pro-ECMO group, although this difference was not statistically significant (64.1% vs. 82.4%, log-rank P = 0.152; 46.5% vs. 72.1%, log-rank P = 0.182, respectively). After regrouping based on the reason for ECMO support, 30-day survival was satisfactory, while 90-day survival was poor in patients who received ECMO as a bridge to transplantation. However, prophylactic intraoperative use of ECMO and post-operative ECMO prolongation demonstrated promising survival and acceptable complication rates. In particular, patients who initially received venovenous (VV) ECMO intraoperatively with the same configuration post-operatively achieved excellent outcomes. The use of ECMO to salvage a graft affected by severe PGD also achieved acceptable survival in the rescue group. Conclusions: Prophylactic intraoperative ECMO support and post-operative ECMO prolongation demonstrated promising survival outcomes and acceptable complications in LTx patients. Particularly, VV ECMO provided safe and effective support intraoperatively and prophylactic prolongation reduced the incidence of PGD in selected patients. However, since this study was conducted in a relatively low-volume transplant center, further studies are needed to validate the results.

A novel LC-MS/MS method for mepivacaine determination and pharmacokinetic study in a single-dose two-period crossover in healthy subjects.

The objective of this work was to develop a simple, selective, and sensitive LC-MS/MS method for the quantitation of the mepivacaine in Chinese biological matrix. The calibration curve of mepivacaine ranged from 0.5 to 2000 ng/mL with the lower limit of quantitation being 0.5 ng/mL. This sensitivity was high enough to describe the profile of blood mepivacaine level versus time. Thereby it was very desirable for the pharmacokinetic study because of its high sensitivity and accuracy. The study used a single-dose two-period crossover design principle. For the pharmacokinetic analysis of plasma, the mean (SD) values obtained were as follows: t1/2, 1.63 (0.43) h; Cmax, 435.3 (67.4) ng/ml; AUC0-t, 1546.9 (339.7) ng/ml·h; AUC0-∞, 1982.3 (421.4) ng/ml·h; Tmax, 0.62 (0.31) h. The validated method has been successfully applied to assess the pharmacokinetic study of mepivacaine after a single administration to Chinese volunteers.