Ultrasound-guided serratus anterior plane block to prevent neurocognitive impairment in elderly patients after thoracoscopic lobectomy: protocol for a single-centre, double-blind, randomised controlled trial.

INTRODUCTION: Postoperative neurocognitive dysfunction (PND), including postoperative delirium (POD), is a common complication in elderly patients after major surgeries, often leading to poor postoperative recovery. Although the pathological mechanism underlying PND is still unclear, postoperative pain is strongly associated with the development of PND. The ultrasound-guided serratus anterior plane block (SAPB) has been reported to relieve postoperative pain in thoracic surgery. Therefore, this prospective trial hypothesises that SAPB may reduce the incidence of PND in the elderly undergoing thoracoscopic lobectomy. METHODS AND ANALYSIS: This study is designed as a single-centre, double-blind, randomised controlled clinical trial. A total of 256 elderly patients scheduled to undergo thoracoscopic lobectomy at Shanghai Pulmonary Hospital will be randomly assigned to general anaesthesia group or SAPB group. The primary outcome is the incidence of PND 7 days postoperatively or before discharge from hospital. The secondary outcomes include the occurrence of POD, the postoperative pain scores, Quality of Recovery at 1-2 days postoperatively and incidence of PND at 3 months postoperatively. The levels of fasting blood glucose in peripheral blood will be examined before and 1-2 days postoperatively. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research Ethics Committee of Shanghai Pulmonary Hospital (identifier: K20-290). All participants will be required to provide written informed consent before any protocol-specific procedures. Findings will be disseminated in a peer-reviewed journal and in national and/or international meetings to guide future practice. TRIAL REGISTRATION NUMBER: ChiCTR2100052633.

Compatibility Study of Peptide and Glycerol Using Chromatographic and Spectroscopic Techniques: Application to a Novel Antimicrobial Peptide Cbf-14 Gel.

The interactions between active pharmaceutical ingredients (APIs) and excipients may lead to API degradation, thereby affecting the safety and efficacy of drug products. Cbf-14 is a synthetic peptide derived from Cathelicidin-BF, showing potential for bacterial and fungal infections. In order to assess impurities in Cbf-14 gel, we developed a two-dimensional liquid chromatography coupled with quadrupole/time-of-flight mass spectrometric method. A total of eleven peptide degradation impurities were identified and characterized. Furthermore, the compatibility tests were conducted to evaluate the interactions of Cbf-14 with glycerol and methylcellulose, respectively. The results revealed that the impurities originated from condensation reactions between Cbf-14 and aldehydes caused by glycerol degradation. Several aldehydes were employed to validate this hypothesis. The formation mechanisms were elucidated as Maillard reactions between primary amino groups of Cbf-14 and aldehydes derived from glycerol degradation. Additionally, the compatibility of Cbf-14 with glycerol from different sources and with varying storage times was investigated. Notably, the interaction products in the gel increased with extended storage time, even when fresh glycerol for injection was added. This study offers unique insights into the compatibility study of peptides and glycerol, contributing to the ongoing quality study of Cbf-14 gel. It also serves as a reference for the design of other peptide preparations and excipients selections.

Comparation between novel online models and the AJCC 8th TNM staging system in predicting cancer-specific and overall survival of small cell lung cancer.

Background: Most of previous studies on predictive models for patients with small cell lung cancer (SCLC) were single institutional studies or showed relatively low Harrell concordance index (C-index) values. To build an optimal nomogram, we collected clinicopathological characteristics of SCLC patients from Surveillance, Epidemiology, and End Results (SEER) database. Methods: 24,055 samples with SCLC from 2010 to 2016 in the SEER database were analyzed. The samples were grouped into derivation cohort (n=20,075) and external validation cohort (n=3,980) based on America's different geographic regions. Cox regression analyses were used to construct nomograms predicting cancer-specific survival (CSS) and overall survival (OS) using derivation cohort. The nomograms were internally validated by bootstrapping technique and externally validated by calibration plots. C-index was computed to compare the accuracy and discrimination power of our nomograms with the 8th of version AJCC TNM staging system and nomograms built in previous studies. Decision curve analysis (DCA) was applied to explore whether the nomograms had better clinical efficiency than the 8th version of AJCC TNM staging system. Results: Age, sex, race, marital status, primary site, differentiation, T classification, N classification, M classification, surgical type, lymph node ratio, radiotherapy, and chemotherapy were chosen as predictors of CSS and OS for SCLC by stepwise multivariable regression and were put into the nomograms. Internal and external validations confirmed the nomograms were accurate in prediction. C-indexes of the nomograms were relatively satisfactory in derivation cohort (CSS: 0.761, OS: 0.761) and external validation cohort (CSS: 0.764, OS: 0.764). The accuracy of the nomograms was superior to that of nomograms built in previous studies. DCA showed the nomograms conferred better clinical efficiency than 8th version of TNM staging system. Conclusions: We developed practical nomograms for CSS (https://guowei2020.shinyapps.io/DynNom-CSS-SCLC/) and OS (https://drboidedwater.shinyapps.io/DynNom-OS-SCLC/) prediction of SCLC patients which may facilitate clinicians in individualized therapeutics.

4-octyl itaconate ameliorates alveolar macrophage pyroptosis against ARDS via rescuing mitochondrial dysfunction and suppressing the cGAS/STING pathway.

Acute respiratory distress syndrome (ARDS) is a high-mortality pulmonary disorder characterized by an intense inflammatory response and a cytokine storm. As of yet, there is no proven effective therapy for ARDS. Itaconate, an immunomodulatory derivative accumulated during inflammatory macrophage activation, has attracted widespread attention for its potent anti-inflammatory and anti-oxidative properties. This study pointed to explore the protective impacts of 4-octyl itaconate (4-OI) on ARDS. The results showed that lung injury was attenuated markedly after 4-OI pre-treatment, as represented by decreased pulmonary edema, inflammatory cell infiltration, and production of inflammatory factors. LPS stimulation induced NLRP3-mediated pyroptosis in vitro and in vivo, as represented by the cleavage of gasdermin D (GSDMD), IL-18 and IL-1ß release, and these changes could be prevented by 4-OI pretreatment. Mechanistically, 4-OI eliminated mitochondrial reactive oxygen species (mtROS) and mtDNA escaping to the cytosol through the opening mitochondrial permeability transition pore (mPTP) in alveolar macrophages (AMs) under oxidative stress. In addition, 4-OI pretreatment markedly downregulated cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) expression, and interferon regulatory factor 3 (IRF3) phosphorylation in vitro and in vivo. Meanwhile, inhibition of STING/IRF3 pathway alleviated NLRP3-mediated pyroptosis induced by LPS in vitro. Taken together, this study indicated that 4-OI ameliorated ARDS by rescuing mitochondrial dysfunction and inhibiting NLRP3-mediated macrophage pyroptosis in a STING/IRF3-dependent manner, which further revealed the potential mechanism of itaconate in preventing inflammatory diseases.

A Randomized Study of Rigid Video Stylet versus Macintosh Laryngoscope for Double-Lumen Endobronchial Tube Intubation Assistance in Thoracoscopic Pulmonary Surgery.

Double-lumen endobronchial tube (DLT) intubation is more challenging than single-lumen tube intubation is, and the rigid video stylet (RVS) is one of the tools that has emerged to deal with this demanding intubation procedure. We evaluated whether the UE® RVS can shorten the DLT intubation time and improve the first-attempt intubation success rate compared with that of Macintosh laryngoscope (ML). A total of 130 participants scheduled to undergo thoracoscopic pulmonary surgeries were enrolled. They were randomized to receive either ML- or RVS-assisted DLT intubation. The primary outcomes were the intubation time and first-attempt intubation success rate. The secondary outcomes were the overall intubation success rate, mean arterial pressure, postoperative sore throat (POST), and postoperative hoarseness at 1 h and 24 h. Compared with the ML group, the intubation time was significantly shorter in the RVS group (p < 0.001; 30.82 ± 10.61 vs. 39.62 ± 6.54 s), however, the first-attempt success rate was significantly lower (p = 0.048; 83.08% vs. 95.16%). The POST at 1 h was less severe in the RVS group (p = 0.021). No significant differences were found for the other indicators. Among the patients with normal airways, the UE® RVS can achieve faster DLT intubation and decrease the severity of a POST at 1 h, although it was associated with a lower first-attempt intubation success rate.

Research trends in ferroptosis since the origin of the concept: A bibliometric analysis.

Ferroptosis is a newly characterized form of regulated cell death. This bibliometric analysis identified the scientific output, leading institutions and research teams, current research hotspots and trends in research on ferroptosis since the origin of the concept. We searched the Science Citation Index Expanded of Web of Science Core Collection for papers on ferroptosis up to 3 June 2022. The acquired data were analysed and visualized by Bibliometrix package and VOSviewer. The study ultimately included 3511 relevant papers, and annual production in this field has grown rapidly in recent years. Institutions and scholars from China contributed the most work, but the impact of their research was much less than that of the United States. Prof. Brent R. Stockwell's team from Columbia University in the United States has a very strong academic influence in the field. Front Cell Dev Biol published the most papers in the field of ferroptosis. As the keywords of the papers in this field changed from the most numerous 'oxidative stress', 'cell-death', 'iron', 'expression', and 'lipid-peroxidation', to 'prognosis', 'immunotherapy', 'progression', 'tumour microenvironment', and 'colorectal cancer', the hotspot of ferroptosis research is gradually shifting from basic research to clinical translational research. The mechanism of tumour formation and treatment will become the frontier in the field of ferroptosis research in the future.

Construction and validation of nomograms based on the log odds of positive lymph nodes to predict the prognosis of lung neuroendocrine tumors.

Background: This research aimed to investigate the predictive performance of log odds of positive lymph nodes (LODDS) for the long-term prognosis of patients with node-positive lung neuroendocrine tumors (LNETs). Methods: We collected 506 eligible patients with resected N1/N2 classification LNETs from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The study cohort was split into derivation cohort (n=300) and external validation cohort (n=206) based on different geographic regions. Nomograms were constructed based on the derivation cohort and validated using the external validation cohort to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS) of patients with LNETs. The accuracy and clinical practicability of nomograms were tested by Harrell's concordance index (C-index), integrated discrimination improvement (IDI), net reclassification improvement (NRI), calibration plots, and decision curve analyses. Results: The Cox proportional-hazards model showed the high LODDS group (-0.79≤LODDS) had significantly higher mortality compared to those in the low LODDS group (LODDS<-0.79) for both CSS and OS. In addition, age at diagnosis, sex, histotype, type of surgery, radiotherapy, and chemotherapy were also chosen as predictors in Cox regression analyses using stepwise Akaike information criterion method and included in the nomograms. The values of C-index, NRI, and IDI proved that the established nomograms were better than the conventional eighth edition of the TNM staging system. The calibration plots for predictions of the 1-, 3-, and 5-year CSS/OS were in excellent agreement. Decision curve analyses showed that the nomograms had value in terms of clinical application. Conclusions: We created visualized nomograms for CSS and OS of LNET patients, facilitating clinicians to bring individually tailored risk assessment and therapy.

Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Fatty acid metabolism takes part in malignancy progression. However, the roles fatty acid metabolism plays in LUAD are still unclear. Methods: The transcriptomic and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were extracted. ssGSEA, WGCNA, univariable Cox regression, and LASSO Cox regression analyses were performed to identify the fatty acid metabolism-related genes which influenced the overall survival (OS) and build a fatty acid-related risk score (FARS) model. A nomogram was established based on the FARS and other clinicopathological features, and ROC and calibration plots were used to validate the prediction accuracy. The tumor microenvironment (TME) of patients with high and low FARS was compared. Results: A total of 38 genes were identified to be independently related to the survival outcome and put into a FARS model. High FARS patients exhibited significantly worse OS. The nomogram included the FARS and pathological stage, and the AUC of the nomogram predicting 1-, 2-, 3-, 4-, and 5-year OS was 0.789, 0.807, 0.798, 0.809, and 0.753, respectively. Calibration plots also indicated good accuracy. Moreover, the samples of the high FARS had higher expression of PDL1. Conclusion: We constructed a FARS model which could accurately predict the survival outcome of the LUAD patients. The genes of the FARS are related to the tumor microenvironment and patients with high FARS can potentially benefit more from anti-PD1/PDL1 immunotherapy. In addition, the mechanisms of the genes in the FARS affecting prognosis are worthy of further research to develop new gene-targeted drugs.

Role of Pneumonectomy in T1-4N2M0 Non-Small Cell Lung Cancer: A Propensity Score Matching Analysis.

Background: N2 stage disease constitutes approximately 20%-30% of all non-small cell lung cancer (NSCLC). Concurrently, surgery remains the first-choice treatment for patients with N2 NSCLC if feasible. However, the role of pneumonectomy in N2 NSCLC has rarely been investigated and remains controversial. Methods: We enrolled 26,798 patients with T1-4N2M0 NSCLC (stage IIIA/IIIB) from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. We compared the overall survival (OS) and cancer-specific survival (CSS) between patients who received pneumonectomy and those who did not receive surgery. The Kaplan-Meier method, Cox regression analyses, and propensity score matching (PSM) were applied to demonstrate the effect of pneumonectomy. Results: Patients receiving pneumonectomy had a significantly better OS and CSS than those without pneumonectomy both before [adjusted-HR (95% CI): 0.461 (0.425-0.501) for OS, 0.444 (0.406-0.485) for CSS] and after PSM [adjusted-HR (95% CI): 0.499 (0.445-0.560) for OS, 0.457 (0.405-0.517) for CSS] with all p-values <0.001. Subgroup analysis demonstrated concordant results stratified by demographic or clinicopathological variables. In sensitivity analysis, no significant difference was observed between patients receiving single pneumonectomy and chemoradiotherapy without surgery in OS and CSS both before [unadjusted-HR (95% CI): 1.016 (0.878-1.176) for OS, 0.934 (0.794-1.099) for CSS, p = 0.832] and after PSM [unadjusted-HR (95% CI): 0.988 (0.799-1.222) for OS, 0.938 (0.744-1.182) for CSS] with all p-values >0.4. Conclusion: For patients with T1-4N2M0 NSCLC (stage IIIA/IIIB), pneumonectomy is an independent protective factor of OS and should be considered when applicable.

A Bibliometric Analysis of the Innate Immune DNA Sensing cGAS-STING Pathway from 2013 to 2021.

Background and aims: Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) are key components of the innate immune system. This study aims to evaluate the research of cGAS-STING pathway and predict the hotspots and developing trends in this field using bibliometric analysis. Methods: We retrieved publications from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) in 1975-2021 on 16 March 2022. We examined the retrieved data by bibliometrix package in R software, VOSviewer and CiteSpace were used for visualizing the trends and hotspots of research on the cGAS-STING pathway. Results: We identified 1047 original articles and reviews on the cGAS-STING pathway published between 1975 and 2021. Before 2016, the publication trend was increasing steadily, but there was a significant increase after 2016. The United States of America (USA) produced the highest number of papers (Np) and took the highest number of citations (Nc), followed by China and Germany. The University of Texas System and Frontiers in Immunology were the most prolific affiliation and journal respectively. In addition, collaboration network analysis showed that there were tight collaborations among the USA, China and some European countries, so the top 10 affiliations were all from these countries and regions. The paper published by Sun LJ in 2013 reached the highest local citation score (LCS). Keywords co-occurrence and co-citation cluster analysis revealed that inflammation, senescence, and tumor were popular terms related to the cGAS-STING pathway recently. Keywords burst detection suggested that STING-dependent innate immunity and NF-κB-dependent broad antiviral response were newly-emerged hotspots in this area. Conclusions: This bibliometric analysis shows that publications related to the cGAS-STING pathway tend to increase continuously. The research focus has shifted from the mechanism how cGAS senses dsDNA and cGAMP binds to STING to the roles of the cGAS-STING pathway in different pathological state.

A Novel Strategy for Predicting 72-h Mortality After Admission in Patients With Polytrauma: A Study on the Development and Validation of a Web-Based Calculator.

Background: Early and accessible screening of patients with polytrauma at a high risk of hospital death is essential. The purpose of this research was to seek an accurate and convenient solution to predict deaths occurring within 72 h after admission of these patients. Methods: A secondary analysis was conducted on 3,075 patients with polytrauma from the Dryad database. We imputed missing values in eligible individuals with the k-nearest neighbor algorithm and then randomly stratified them into the training group (n = 2,461) and the validation group (n = 614) based on a proportion of 8:2. The restricted cubic spline, univariate, backward stepwise, and multivariate logistic regression methods were employed to determine the suitable predictors. Calibration and receiver operating characteristic (ROC) curves were applied to assess the calibration and discrimination of the obtained model. The decision curve analysis was then chosen as the measure to examine the clinical usage. Results: Age, the Glasgow Coma Scale score, the Injury Severity Score, base excess, and the initial lactate level were inferred as independent prognostic factors related to mortality. These factors were then integrated and applied to construct a model. The performance of calibration plots, ROC curves, and decision curve analysis indicated that the model had satisfactory predictive power for 72-h mortality after admission of patients with polytrauma. Moreover, we developed a nomogram for visualization and a web-based calculator for convenient application (https://songandwen.shinyapps.io/DynNomapp/). Conclusions: A convenient web-based calculator was constructed to robustly estimate the risk of death in patients with polytrauma within 72 h after admission, which may aid in further rationalization of clinical decision-making and accurate individual treatment.

Magnesium Hydride Ameliorates Endotoxin-Induced Acute Respiratory Distress Syndrome by Inhibiting Inflammation, Oxidative Stress, and Cell Apoptosis.

Acute respiratory distress syndrome (ARDS) causes uncontrolled pulmonary inflammation, resulting in high morbidity and mortality in severe cases. Given the antioxidative effect of molecular hydrogen, some recent studies suggest the potential use of molecular hydrogen as a biomedicine for the treatment of ARDS. In this study, we aimed to explore the protective effects of magnesium hydride (MgH2) on two types of ARDS models and its underlying mechanism in a lipopolysaccharide (LPS)-induced ARDS model of the A549 cell line. The results showed that LPS successfully induced oxidative stress, inflammatory reaction, apoptosis, and barrier breakdown in alveolar epithelial cells (AEC). MgH2 can exert an anti-inflammatory effect by down-regulating the expressions of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). In addition, MgH2 decreased oxidative stress by eliminating intracellular ROS, inhibited apoptosis by regulating the expressions of cytochrome c, Bax, and Bcl-2, and suppressed barrier breakdown by up-regulating the expression of ZO-1 and occludin. Mechanistically, the expressions of p-AKT, p-mTOR, p-P65, NLRP3, and cleaved-caspase-1 were decreased after MgH2 treatment, indicating that AKT/mTOR and NF-κB/NLRP3/IL-1ß pathways participated in the protective effects of MgH2. Furthermore, the in vivo study also demonstrated that MgH2-treated mice had a better survival rate and weaker pathological damage. All these findings demonstrated that MgH2 could exert an ARDS-protective effect by regulating the AKT/mTOR and NF-κB/NLRP3/IL-1ß pathways to suppress LPS-induced inflammatory reaction, oxidative stress injury, apoptosis, and barrier breakdown, which may provide a potential strategy for the prevention and treatment of ARDS.

Study on the Effect and Mechanism of Huaji Jianpi Decoction on Simple Obesity.

Background: As the major type of obesity in clinical, simple obesity has gained increasing attention in recent years. Depending on the etiology and pathogenesis of simple obesity and combined with clinical practice experience, Huaji Jianpi decoction (HJJPD) was established to invigorate the spleen and eliminate dampness; however, the underlying molecular mechanism is yet unclear. Materials and Methods: A simple obesity mouse model was established by feeding a high-fat diet to the animals, and the related indexes were analyzed. The mice were divided into the normal, positive control (orlistat), and HJJPD high-dose, medium-dose, and low-dose groups. After 6 weeks of administration, the curative effect of HJJPD was observed. Simple obesity is associated with leptin resistance. The leptin signal transduction pathways mainly include the JAK2-STAT3, AMPK-ACC, LepRb-IRS-PI3K-PDE3B-cAMP, and LepRb-SHP2-MAPKs (ERK1/2) pathways. Therefore, the networks of HJJPD acting on these four pathway-related targets were constructed using the network pharmacology method, and the key nodes were identified. Results: After 6 weeks of drug intervention, we found a good therapeutic effect of HJJPD on simple obesity in the mouse model. The biological network analysis showed that HJJPD plays a role in treating leptin resistance in simple obesity by acting on multiple targets in the JAK2-STAT3 pathway via various components. Also, HJJPD can improve leptin resistance in mice by enhancing the binding force of LEP and LEPRB and activating the LEP-mediated JAK2-STAT3 signaling pathway. Conclusion: In this study, animal experiments, network pharmacology, and molecular biology were combined to establish a mouse model of simple obesity, confirm the role of HJJPD in the treatment of simple obesity, and preliminarily reveal the related mechanism. Relevant research results will provide a basis for the treatment of simple obesity and the drug discovery.

A bibliometric analysis of autophagy in lung diseases from 2012 to 2021.

Background: Autophagy refers to the process in which cells wrap their damaged organelles or unwanted proteins into a double-membrane structure and direct them to lysosomes for degradation. Autophagy can regulate many lung diseases such as pulmonary hypertension, acute lung injury, and lung cancer. However, few bibliometric studies on autophagy are available. The aim of the present study was to clarify the role of autophagy in lung diseases by bibliometric analysis. Methods: Publications were retrieved from the 2012-2021 Science Citation Index Expanded of Web of Science Core Collection on 20 September 2022. Bibliometrix package in R software was used for data retrieval. VOSviewer and CiteSpace were used to visualize the research focus and trend regarding the effect of autophagy on lung disease. Results: A total of 4,522 original articles and reviews on autophagy in lung diseases published between 2012 and 2021 were identified. China had the largest number of published papers and citations, whereas the United States (US) ranked first in the H-index and G-index. Moreover, cooperation network analysis showed close cooperation between the US, China, and some European countries, and the top 10 affiliates were all from these countries and regions. Bibliometric analysis showed that "autophagy" and "apoptosis" were the keywords with the highest frequency. During the past decade, most studies were concerned with basic research on pathways related to the regulatory role of autophagy in the inhibition and attenuation of lung diseases. Conclusion: The study of autophagy in lung diseases is still in the development stage. The information published in these articles has helped researchers understand further the hot spots and development trends in the field more and learn about the collaboration network information regarding authors, countries, and institutions, as well as the paper citation correlation. More studies have been performed to gain deeper insights into the pathogenesis of autophagy by focusing on the links and effects between various diseases. More recently, research in this field has paid increasing attention to the function of autophagy in COVID-19-related lung diseases.

Global Research Trends and Hotspots on Mitochondria in Acute Lung Injury from 2012-2021: A Bibliometric Analysis.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a clinical syndrome associated with mitochondria and lacks effective preventive and therapeutic measures. This bibliometric study aims to gain insight into the scientific findings regarding mitochondria in ALI/ARDS. METHODS: We retrieved the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (WoSCC) for mitochondria in ALI/ARDS publications from 2012-2021. VOSviewer, CiteSpace (5.8. R3) and Bibliometrix (3.1.4) R package were used for further analysis and visualization. RESULT: A total of 756 English-language articles and reviews were identified. The annual number of publications presented a rapidly developing trend. China was the most productive and cited country, and the USA had the greatest impact. In the keyword co-occurring network, the terms "acute lung injury", "oxidative stress", "inflammation", "mitochondria" and "apoptosis" occurred most frequently. The co-citation network revealed that #1 mesenchymal stromal cell and #3 endothelial cell had the most bursts of citations. In addition, research hotspots have shifted from "potential therapeutic treatments" and "mitochondrial DNA (mtDNA)" to "endothelial cell" and "mesenchymal stromal cell (MSC)". CONCLUSION: This bibliometric analysis reveals the research directions and frontier hotspots of mitochondria in ALI/ARDS, which has shown a rapid growth trend in annual publication numbers. mtDNA, mitophagy, and apoptosis have been the most active research areas, while studies on mitochondrial transfer in stem cells have become a hot topic in recent years.

Predictive value of lymphocyte-to-monocyte ratio in critically Ill patients with atrial fibrillation: A propensity score matching analysis.

BACKGROUND: Inflammation plays a key role in the initiation and progression of atrial fibrillation (AF). Lymphocyte-to-monocyte ratio (LMR) has been proved to be a reliable predictor of many inflammation-associated diseases, but little data are available on the relationship between LMR and AF. We aimed to evaluate the predictive value of LMR in predicting all-cause mortality among AF patients. METHODS: Data of patients diagnosed with AF were retrieved from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. X-tile analysis was used to calculate the optimal cutoff value for LMR. The Cox regression model was used to assess the association of LMR and 28-day, 90-day, and 1-year mortality. Additionally, a propensity score matching (PSM) method was performed to minimize the impact of potential confounders. RESULTS: A total of 3567 patients hospitalized with AF were enrolled in this study. The X-tile software indicated that the optimal cutoff value of LMR was 2.67. A total of 1127 pairs were generated, and all the covariates were well balanced after PSM. The Cox proportional-hazards model showed that patients with the low LMR (≤2.67) had a higher 1-year all-cause mortality than those with the high LMR (>2.67) in the study cohort before PSM (HR = 1.640, 95% CI: 1.437-1.872, p < 0.001) and after PSM (HR = 1.279, 95% CI: 1.094-1.495, p = 0.002). The multivariable Cox regression analysis for 28-day and 90-day mortality yielded similar results. CONCLUSIONS: The lower LMR (≤2.67) was associated with a higher risk of 28-day, 90-day, and 1-year all-cause mortality, which might serve as an independent predictor in AF patients.

Lobectomy Versus Sublobectomy in Stage IIIA/N2 Non-Small Cell Lung Cancer: A Population-Based Study.

BACKGROUND: The role lobectomy plays in stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial for a long time. What's more, no previous study concentrates on whether sublobectomy can improve survival outcome for these patients, so we performed this population-based study to investigate whether stage IIIA/N2 NSCLC can benefit from these two surgery types and compare survival outcomes after lobectomy and sublobectomy. METHODS: A total of 21,638 patients diagnosed with stage IIIA/N2 NSCLC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database matched our selection criteria. The study cohort included patients who received no surgery (n = 15,951), sublobectomy (n = 628) and lobectomy (n = 5,059). Kaplan-Meier method, Cox regression analyses, and inverse probability of treatment weighting (IPTW)-adjusted Cox regression were used to illustrate the influence of sublobectomy and lobectomy on overall survival (OS) rates in the study cohort and compare these two surgery types. RESULTS: Multivariable Cox regression analysis showed sublobectomy [HR: 0.584 (95%CI: 0.531-0.644), P-value <0.001; IPTW-adjusted HR: 0.619 (95%CI: 0.605-0.633), P-value <0.001] and lobectomy [HR: 0.439 (95%CI: 0.420-0.459), P-value <0.001; IPTW-adjusted HR: 0.441 (95%CI: 0.431-0.451), P-value <0.001] were both related to better OS rates compared with no surgery, and lobectomy exhibited better survival than sublobectomy [HR: 0.751 (95%CI: 0.680-0.830), P-value <0.001; IPTW-adjusted HR: 0.713 (95%CI: 0.696-0.731), P-value <0.001]. Moreover, the results in subgroup analyses based on age, tumor size and radiotherapy and chemotherapy strategy in all study cohort were consistent. CONCLUSION: Stage IIIA/N2 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provided better OS rates than sublobectomy.

Dynamic nomograms combining N classification with ratio-based nodal classifications to predict long-term survival for patients with lung adenocarcinoma after surgery: a SEER population-based study.

BACKGROUND: The prognostic roles of three lymph node classifications, number of positive lymph nodes (NPLN), log odds of positive lymph nodes (LODDS), and lymph node ratio (LNR) in lung adenocarcinoma are unclear. We aim to find the classification with the strongest predictive power and combine it with the American Joint Committee on Cancer (AJCC) 8th TNM stage to establish an optimal prognostic nomogram. METHODS: 25,005 patients with T1-4N0-2M0 lung adenocarcinoma after surgery between 2004 to 2016 from the Surveillance, Epidemiology, and End Results database were included. The study cohort was divided into training cohort (13,551 patients) and external validation cohort (11,454 patients) according to different geographic region. Univariate and multivariate Cox regression analyses were performed on the training cohort to evaluate the predictive performance of NPLN (Model 1), LODDS (Model 2), LNR (Model 3) or LODDS+LNR (Model 4) respectively for cancer-specific survival and overall survival. Likelihood-ratio χ2 test, Akaike Information Criterion, Harrell concordance index, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to evaluate the predictive performance of the models. Nomograms were established according to the optimal models. They're put into internal validation using bootstrapping technique and external validation using calibration curves. Nomograms were compared with AJCC 8th TNM stage using decision curve analysis. RESULTS: NPLN, LODDS and LNR were independent prognostic factors for cancer-specific survival and overall survival. LODDS+LNR (Model 4) demonstrated the highest Likelihood-ratio χ2 test, highest Harrell concordance index, and lowest Akaike Information Criterion, and IDI and NRI values suggested Model 4 had better prediction accuracy than other models. Internal and external validations showed that the nomograms combining TNM stage with LODDS+LNR were convincingly precise. Decision curve analysis suggested the nomograms performed better than AJCC 8th TNM stage in clinical practicability. CONCLUSIONS: We constructed online nomograms for cancer-specific survival and overall survival of lung adenocarcinoma patients after surgery, which may facilitate doctors to provide highly individualized therapy.

Role of Ferroptosis in Lung Diseases.

Ferroptosis is a new type of programmed cell death characterized by intracellular iron accumulation and lipid peroxidation that leads to oxidative stress and cell death. The metabolism of iron, lipids, and amino acids and multiple signalling pathways precisely regulate the process of ferroptosis. Emerging evidence has demonstrated that ferroptosis participates in the occurrence and progression of various pathological conditions and diseases, such as infections, neurodegeneration, tissue ischaemia-reperfusion injury and immune diseases. Recent studies have also indicated that ferroptosis plays a critical role in the pathogenesis of acute lung injury, chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary infection and asthma. Herein, we summarize the latest knowledge on the regulatory mechanism of ferroptosis and its association with iron, lipid and amino acid metabolism as well as several signalling pathways. Furthermore, we review the contribution of ferroptosis to the pathogenesis of lung diseases and discuss ferroptosis as a novel therapeutic target for various lung diseases.

[Research progress of metabolism reprogramming in regulating macrophage polarization].

Macrophages are important innate immune cells that play essential roles in the inflammatory response. The phenotypic plasticity of macrophages enables them to be polarized into distinct gene phenotypes under different immune microenvironments to regulate the process of inflammation. The study of macrophage metabolic reprogramming aims to clarify the influence of key metabolic pathways on the regulation of different polarization states and related functions of macrophages. This review focuses on the relationship between the four key metabolic pathways [glycolysis, tricarboxylic acid (TCA) cycle, fatty acid metabolism and amino acid metabolism] and the distinct gene phenotypes of macrophages. It also reveals the metabolic regulation of the immune function of macrophage cells thus to provide new ideas and methods for the study of macrophage polarization-related process of inflammation.