GLUT3-mediated cigarette smoke-induced epithelial-mesenchymal transition in chronic obstructive pulmonary disease through the NF-kB/ZEB1 pathway.

BACKGROUND: Airway remodelling plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) is a significant process during the occurrence of airway remodelling. Increasing evidence suggests that glucose transporter 3 (GLUT3) is involved in the epithelial mesenchymal transition (EMT) process of various diseases. However, the role of GLUT3 in EMT in the airway epithelial cells of COPD patients remains unclear. METHODS: We detected the levels of GLUT3 in the peripheral lung tissue of COPD patients and cigarette smoke (CS)-exposed mice. Two Gene Expression Omnibus GEO datasets were utilised to analyse GLUT3 gene expression profiles in COPD. Western blot and immunofluorescence were used to detect GLUT3 expression. In addition, we used the AAV9-GLUT3 inhibitor to reduce GLUT3 expression in the mice model. Masson's staining and lung function measurement were used detect the collagen deposition and penh in the mice. A cell study was performed to confirm the regulatory effect of GLUT3. Inhibition of GLUT3 expression with siRNA, Western blot, and immunofluorescence were used to detect the expression of E-cadherin, N-cadherin, vimentin, p65, and ZEB1. RESULTS: Based on the GEO data set analysis, GLUT3 expression in COPD patients was higher than in non-smokers. Moreover, GLUT3 was highly expressed in COPD patients, CS exposed mice, and BEAS-2B cells treated with CS extract (CSE). Further research revealed that down-regulation of GLUT3 significantly alleviated airway remodelling in vivo and in vitro. Lung function measurement showed that GLUT3 reduction reduced airway resistance in experimental COPD mice. Mechanistically, our study showed that reduction of GLUT3 inhibited CSE-induced EMT by down-regulating the NF-κB/ZEB1 pathway. CONCLUSION: We demonstrate that CS enhances the expression of GLUT3 in COPD and further confirm that GLUT3 may regulate airway remodelling in COPD through the NF-κB/ZEB1 pathway; these findings have potential value in the diagnosis and treatment of COPD. The down-regulation of GLUT3 significantly alleviated airway remodelling and reduced airway resistance in vivo. Our observations uncover a key role of GLUT3 in modulating airway remodelling and shed light on the development of GLUT3-targeted therapeutics for COPD.

Stenotrophomonas maltophilia contributes to smoking-related emphysema through IRF1-triggered PANoptosis of alveolar epithelial cells.

Cigarette smoke (CS), the main source of indoor air pollution and the primary risk factor for respiratory diseases, contains chemicals that can perturb microbiota through antibiotic effects. Although smoking induces a disturbance of microbiota in the lower respiratory tract, whether and how it contributes to initiation or promotion of emphysema are not well clarified. Here, we demonstrated an aberrant microbiome in lung tissue of patients with smoking-related COPD. We found that Stenotrophomonas maltophilia (S. maltophilia) was expanded in lung tissue of patients with smoking-related COPD. We revealed that S. maltophilia drives PANoptosis in alveolar epithelial cells and represses formation of alveolar organoids through IRF1 (interferon regulatory factor 1). Mechanistically, IRF1 accelerated transcription of ZBP1 (Z-DNA Binding Protein 1) in S. maltophilia-infected alveolar epithelial cells. Elevated ZBP1 served as a component of the PANoptosome, which triggered PANoptosis in these cells. By using of alveolar organoids infected by S. maltophilia, we found that targeting of IRF1 mitigated S. maltophilia-induced injury of these organoids. Moreover, the expansion of S. maltophilia and the expression of IRF1 negatively correlated with the progression of emphysema. Thus, the present study provides insights into the mechanism of lung dysbiosis in smoking-related COPD, and presents a potential target for mitigation of COPD progression.

IFN-γ decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3ß signaling pathway.

Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8+ T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8+ T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3ß may regulate the INF-γ/PD-1 axis in CD8+ T cells from COVID-19 convalescent patients. In parallel, an IFN-γ neutralizing antibody reduced AKT and increased GSK3ß in PBMCs. An AKT agonist (SC79) significantly decreased p-GSK3ß. Moreover, AKT decreased PD-1 on CD8+ T cells, and GSK3ß increased PD-1 on CD8+ T cells according to flow cytometry analysis. Collectively, we demonstrated that recovered COVID-19 patients may develop long COVID. Increased IFN-γ in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8+ T cells by regulating the AKT/GSK3ß signaling pathway.

Association of radiological severity of hip involvement with clinical characteristics and sagittal spinopelvic balance in patients with ankylosing spondylitis.

INTRODUCTION: This is the first study to analyze the associations between the radiological severity of hip involvement with clinical characteristics and sagittal spinopelvic balance in patients with ankylosing spondylitis (AS). METHOD: We evaluated 182 patients with AS who were referred to outpatient clinics. Patient demographic data and clinical and radiographic parameters were collected. Patients were divided into three groups based on the Bath Ankylosing Spondylitis Radiology Hip Index. Clinical characteristics and spinopelvic parameters acquired by a low-dose biplanar imaging system were evaluated among these groups. RESULTS: Patients with more severe hip involvement were older and had longer disease duration and diagnostic delay, with lower Harris Hip Score (p < 0.001) and 12-item Short Form Health Survey Physical Component Score (p < 0.001) and higher Bath Ankylosing Spondylitis Disease Activity Index (p = 0.030) and Functional Index (p < 0.001). Patients with more severe hip involvement had significantly higher sacroiliac grade (p < 0.001) and higher modified Stoke Ankylosing Spondylitis Spinal Score (p < 0.001). Patients with moderate and severe hip involvement had similar lumbar lordosis and spino-sacral angle, whereas patients with severe hip involvement had lower pelvic tilt, pelvic femoral angle, higher sacral slope, and sagittal vertical axis. CONCLUSIONS: The severity of hip involvement is associated with physical function and is not consistent with the severity of spinal involvement. Severe hip involvement impairs the ability to retrovert the pelvis to accommodate the sagittal deformity, and spinopelvic parameters should be concretely evaluated in preoperative counseling of patients with AS waiting for total hip arthroplasty. Key Points • The severity of hip involvement in patients with AS is associated with physical function. • Severe hip involvement impairs the ability to retrovert the pelvis to accommodate the sagittal deformity.

CD146 deficiency aggravates chronic obstructive pulmonary disease via the increased production of S100A9 and MMP-9 in macrophages.

Chronic obstructive pulmonary disease (COPD) is a leading cause of global death. As a molecule beyond adhesion, CD146 is involved in COPD pathogenesis. However, the mechanisms of CD146 in COPD remain largely elusive. We hypothesized that CD146 regulates the production of matrix metalloproteinase-9 (MMP-9) in macrophages and thereby contributes to COPD. Here, we constructed a murine model of COPD using lipopolysaccharide (LPS) and porcine pancreatic elastase (PPE). In COPD-like mice, LPS and PPE decreased the pulmonary expression of CD146. MMP-9 expression and bioactivity were increased in CD146 knockout COPD-like mice. In vitro, LPS decreased CD146 expression in macrophages. With or without LPS challenge, CD146-defective macrophages produced more MMP-9. Transcriptome analysis based on next-generation sequencing (NGS) revealed that S100A9 regulated MMP-9 production in CD146-defective macrophages. Targeting S100A9 with paquinimod decreased lung inflammation and alleviated alveolar destruction in COPD-like mice. Collectively, our study suggests that CD146 negatively regulates MMP-9 production in macrophages via the S100A9 pathway in COPD.

A Macrophage-Related Gene Signature for Identifying COPD Based on Bioinformatics and ex vivo Experiments.

Background: This study aims to investigate the association between immune cells and the development of COPD, while providing a new method for the diagnosis of COPD according to the changes in immune microenvironment. Methods: In this study, the "CIBERSORT" algorithm was used to estimate the tissue infiltration of 22 types of immune cells in GSE20257 and GSE10006. The "limma" package was used for differentially expressed analysis. The key modules associated with vital immune cells were identified using WGCNA. GO and KEGG enrichment analysis revealed the biological functions of the candidate genes. Ultimately, a novel diagnostic prediction model was constructed via machine learning methods and multivariate logistic regression analysis based on GSE20257. Furthermore, we examined the stability of the model on one internal test set (GSE10006), three external test sets (GSE8545, GSE57148 and GSE76925), one single-cell transcriptome dataset (GSE167295), macrophages (THP-M cells) and lung tissue from COPD patients. Results: M0 macrophages (AUC > 0.7 in GSE20257 and GSE10006) were considered as the most important immune cells through exploring the immune microenvironment landscapes in COPD patients and healthy controls. The differentially expressed genes from GSE20257 and GSE10006 were divided into six and five modules via WGCNA, respectively. The green module in GSE20257 (cor = 0.41, P < 0.001) and the brown module in GSE10006 (cor = 0.67, P < 0.001) were highly correlated with M0 macrophages and were selected as key modules. Forty-one intersected genes obtained from two modules were primarily involved in regulation of cytokine production, regulation of innate immune response, specific granule, phagosome, lysosome, ferroptosis, and other biological processes. On the basis of the candidate genetic markers further characterized via the "Boruta" and "LASSO" algorithm for COPD, a diagnostic model comprising CLEC5A, FTL and SLC2A3 was constructed, which could accurately distinguish COPD patients from healthy controls in multiple datasets. GSE20257 as the training set has an AUC of 0.916. The AUCs of the internal test set and three external test sets were 0.873, 0.932, 0.675 and 0.688, respectively. Single-cell sequencing analysis suggested that CLEC5A, FTL and SLC2A3 were expressed in macrophages from COPD patients. The expressions of CLEC5A, FTL and SLC2A3 were up-regulated in THP-M cells and lung tissue from COPD patients. Conclusion: According to the variations of immune microenvironment in COPD patients, we constructed and validated a novel macrophage M0-associated diagnostic model with satisfactory predictive value. CLEC5A, FTL and SLC2A3 are expected to be promising targets of immunotherapy in COPD.

Expression Profiles of circRNAs and Identification of hsa_circ_0007608 and hsa_circ_0064656 as Potential Biomarkers for COPD-PH Patients.

Introduction: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), which can worsen the prognosis and increase the mortality of COPD patients. Circular RNA (circRNA) has been discovered to participate in the occurrence and progression of PH in COPD and may have significant prospects for advanced diagnostics and prognosis evaluation. However, the expression profile of circRNAs in human lung tissues with definite diagnosis of COPD-PH remains to be further explored and validated. Methods: Twelve human lung tissue samples (6 each from COPD-PH and control groups) were collected and subjected to high-throughput sequencing. QRT-PCR was performed to validate the differential expression levels of the top 10 dysregulated circRNAs in patients' plasma samples, HPAECs and HPASMCs. Functional and pathway enrichment analysis on target genes was performed to explore the potential functions and pathways of those circRNAs. Hub genes obtained after conducting bioinformatics analysis on the predicted target mRNAs were verified by qRT-PCR in HPAECs and HPASMCs, and then we selected VCAN as a potential key gene involved in the pathogenesis of COPD-PH for immunohistochemistry validation in lung tissue. Results: A total of 136 circRNAs (39 up-regulated and 97 down-regulated) were differentially expressed between the two groups. Following qRT-PCR validation, two circRNAs (hsa_circ_0007608 and hsa_circ_0064656) were believed to be involved in the pathogenesis. GO and KEGG pathway analysis suggested that these two DECs were mainly related to the celluar proliferation, migration and EndMT. PPI network revealed 11 pairs of key mRNAs. VCAM1, VCAN and THBS1, three hub mRNAs with the highest reliability among all, were validated and proven to be up-regulated in COPD-PH. We innovatively found that VCAN may be involved in COPD-PH. Conclusion: This study identified the functional circRNAs, providing insights into the molecular mechanisms and predictions of COPD-PH, and may provide potential diagnostic biomarkers or therapeutic targets for COPD-PH.

Retraction Notice to: METTL3-mediated m6A modification of ZBTB4 mRNA is involved in the smoking-induced EMT in cancer of the lung.

[This retracts the article DOI: 10.1016/j.omtn.2020.12.001.].

Chlamydia psittaci pneumonia in Wuxi, China: retrospective analysis of 55 cases and predictors of severe disease.

Purpose: More and more patients with community-acquired pneumonia have been detected with Chlamydia psittaci (C. psittaci) infected using metagenomic next-generation sequencing (mNGS). Previously, this was unheard of, and several patients presented with severe pneumonia and even required ECMO. We aimed to clarify the clinical characteristics of C. psittaci pneumonia and find out if there are any possible predictors of severe C. psittaci pneumonia. Methods: In this retrospective study, we included all confirmed cases of C. psittaci pneumonia in Wuxi. Epidemiological, clinical, and radiological features, as well as laboratory data, were collected and analyzed. Results: We enrolled 55 patients with C. psittaci pneumonia, with 30 (54.5%) having a history of exposure to birds or their internal organs. 50 (90.9%) patients were diagnosed by mNGS. Patients with C. psittaci pneumonia had many complications, among which, that deserve sufficient attention from clinicians were vascular embolic events (3, 5.5%). High fever was the most common clinical manifestation (41, 74.5%). The majority of patients had a significant increase in neutrophils ratio, neutrophils to lymphocytes ratio (NLR), rapid c-reactive protein, creatine kinase (CK), and lactate dehydrogenase (LDH), as well as a decrease in lymphocytes ratio, albumin, serum sodium, serum potassium, and serum phosphorus. Chest computed tomography scans revealed unilateral pneumonia (70.9%), consolidation (87.3%), air bronchogram (76.4%), and ground-glass opacity (69.1%). The neutrophil ratio, NLR, LDH, and CK were all factors that could identify severe pneumonia. Both AUCs exceeded 0.8; the respective 95% CIs were 0.715-0.944, 0.710-0.963, 0.677-0.937, and 0.718-0.950; all p < 0.05 (0.01, 0.001, 0.007, 0.007 respectively). The ORs were 10.057, 9.750, 10.057, and 9.667, respectively; the 95% CIs were 2.643-38.276, 2.339-40.649, and 2.643-38.276, respectively; all p-values were less than 0.05 (0.001, 0.002, 0.001, 0.001 respectively). Conclusion: C. psittaci pneumonia is a very complex disease that changes all the time. Some patients showed severe pneumonia. Patients will have a poor prognosis if they are not treated promptly and effectively. We discovered that many clinical indicators were typical. Meanwhile, significant increases in neutrophil ratio, NLR, LDH, and CK predicted severe pneumonia. Timely detection of mNGS provided substantial help for clinical diagnosis and early treatment.

Predisposing factors for allogeneic blood transfusion in patients with rheumatoid arthritis undergoing primary unilateral total knee arthroplasty.

Background: To determine the incidence and identify the predisposing factors for allogeneic blood transfusion (ABT) in patients with rheumatoid arthritis (RA) undergoing primary unilateral total knee arthroplasty (TKA). Methods: A total of 702 patients with RA who underwent primary unilateral TKA between 2003 and 2022 at a single center, were retrospectively enrolled. Patients were stratified into the ABT and non-ABT groups. Data on patient demographics, laboratory parameters, and disease- and surgery-related parameters were collected from chart reviews and compared between the ABT and non-ABT groups. Multivariate logistic regression analysis was conducted to identify the possible factors associated with postoperative ABT. Results: A total of 173 (24.6%) patients underwent ABT after surgery. Significant risk factors for ABT included the degree of flexion contracture [odds ratio (OR) = 1.018, P = 0.005] and thickness of insertion (OR = 1.170, P = 0.014). Conversely, body mass index (OR = 0.937, P = 0.018), preoperative hemoglobin level (OR = 0.973, P < 0.001), and intraoperative use of tranexamic acid (TXA) (OR = 0.119, P < 0.001) were associated with a lower risk of ABT in TKA. Conclusion: We identified the significant risk and protective factors for ABT during TKA in patients with RA. This information could be helpful in optimizing perioperative blood management strategies during these surgeries.

Didymodonchangbaiensis (Pottiaceae, Musci), a new species from Changbai Mountain, China and its phylogenetic position based on molecular data.

Changbai Mountain, located in northeast China, is one of the areas with the most complete natural ecosystem preservation in China. A new species, Didymodonchangbaiensis C.Feng, J.Kou, H.-X. Xiao & T.-T.Wu from north slope of Changbai Mountain in Jilin Province of China is described and illustrated. It is characterised by ovate or ovate-lanceolate leaves that are appressed when dry, acute leaf apex, lamina red or reddish-orange with KOH, unistratose lamina throughout, plane and unistratose leaf margins, percurrent costa with one layer of guide cells and without ventral stereids, upper and middle laminal cells with elliptical papillae over the transverse walls between two immediately adjacent cells and basal laminal cells not differentiated from the median cells. Our morphological analyses and molecular results, based on DNA sequences of ITS, rps4 and trnM-trnV, confirm that D.changbaiensis is revealed to be sister to D.daqingii J. Kou, R.H. Zander & C. Feng. This new species is compared with similar species and its phylogenetic position and ecology are discussed.

MicroRNA Let-7 Induces M2 Macrophage Polarization in COPD Emphysema Through the IL-6/STAT3 Pathway.

Background: M2 polarized macrophages are involved in the occurrence and development of emphysema in COPD patients. However, the molecular mechanism of M2 macrophage polarization is still unclear. This study investigated the molecular mechanism of let-7 differentially expressed in bronchial epithelial cells of COPD patients participating in COPD emphysema by regulating the expression of IL-6 and inducing M2 polarization of alveolar macrophages (AM). Materials and Methods: We measured let-7c expression in human lung tissue, serum and the lung tissue of cigarette smoke (CS)-exposed mice by qRT‒PCR. We observed the M1/M2 AM polarization in the lungs of COPD patients and COPD model mice by immunofluorescence analysis. Western blotting was used to determine the expression of MMP9/12 in the lung tissue of COPD patients and CS-exposed mice. An in vitro experiment was performed to determine the molecular mechanism of let-7c-induced macrophage polarization. Results: Let-7c expression was downregulated in COPD patients, CS-exposed mice, and CS extract (CSE)-treated human bronchial epithelial (HBE) cells. AMs in COPD patients and CS-exposed mice were dominated by the M2 type, and the release of MMP9/12 was increased. In vitro, the transfection of mimics overexpressing let-7 or the use of tocilizumab to block signal transduction between HBE cells and macrophages inhibited the IL-6/STAT3 pathway. M2 macrophage polarization was inhibited, and MMP9/12 release was reduced. Conclusion: Our results indicate that CS decreased let-7c expression in HBE cells, and M2 AM polarization was dominant in COPD. In HBE cells, let-7c could inhibit M2 polarization of AMs through the IL-6/STAT3 pathway, providing potential diagnostic and therapeutic value for slowing COPD emphysema.

N6-Methyladenosine-modified circSAV1 triggers ferroptosis in COPD through recruiting YTHDF1 to facilitate the translation of IREB2.

Epithelial cell damage-initiated chronic obstructive pulmonary disease (COPD) is implicated in regulated cell death (RCD) including ferroptosis triggered by complex gene-environment interactions. Our data showed that iron overload and ferroptosis are associated with COPD progression in COPD patients and in experimental COPD. Furthermore, we found that, in lung tissues of COPD patients, circSAV1 was associated with COPD progression by circRNA-seq screening. Knockdown of circSAV1 reversed cigarette smoke extract (CSE)-induced ferroptosis. Mechanistically, m6A-modified circSAV1 formed an RNA-protein ternary complex of circSAV1/YTHDF1/IREB2 to facilitate the translation of IREB2 mRNA. Elevated protein levels of IREB2 disrupted iron homeostasis, resulting in accumulation of a labile iron pool (LIP) and lipid peroxidation, which contribute to ferroptosis. Here we demonstrate, by use of an experimental COPD model induced by cigarette smoke (CS), that silencing of circSAV1 and the treatment with deferoxamine (DFO) blocked CS-induced ferroptosis of lung epithelial cells, which attenuated COPD progression in mice. Our results reveal that N6-methyladenosine-modified circSAV1 triggers ferroptosis in COPD through recruiting YTHDF1 to facilitate the translation of IREB2, indicating that circSAV1 is a mediator of ferroptosis and that circSAV1-dependent ferroptosis is a therapeutic target for COPD. In lung epithelial cell, m6A-modified circSAV1, via recruiting YTHDF1, induces the formation of a circSAV1/YTHDF1/IREB2 mRNA protein ternary complex, which promotes translation of IREB2 mRNA. Further, elevated IREB2 contributes to the accumulation of a labile iron pool (LIP) and lipid peroxidation, then triggers ferroptosis of lung epithelial cells. The ferroptosis of airway epithelial cells and alveolar epithelial cells induces airway remodeling and emphysema, respectively, which causes COPD.

Predisposing factors for allogeneic blood transfusion in patients with ankylosing spondylitis undergoing primary unilateral total hip arthroplasty: a retrospective study.

BACKGROUND: The transfusion rate is relatively high in patients with ankylosing spondylitis (AS) undergoing total hip arthroplasty (THA). However, relevant studies focusing on the predisposing factors for transfusion with a large sample size are lacking. This study aimed to investigate the incidence of and risk factors for allogeneic blood transfusion in patients with AS undergoing primary unilateral THA. METHODS: This retrospective study included 331 patients with AS who underwent primary unilateral THA between 2011 and 2021. Relevant parameters were collected through a chart review. Multivariate logistic regression analysis was conducted to identify possible factors associated with perioperative allogeneic blood transfusion. RESULTS: A total of 113 (34.1%) patients received perioperative allogeneic blood transfusions. Factors related to receiving an allogeneic blood transfusion included prolonged operative duration (odds ratio [OR] per 10 min = 1.139, P = 0.047), increased estimated intraoperative blood loss (OR per 100 mL = 1.348, P < 0.001), and increased postoperative drainage volume (OR per 100 mL = 1.235, P = 0.024). A higher body mass index (BMI) (OR = 0.914, P = 0.012), perioperative tranexamic acid (TXA) use (OR = 0.166, P < 0.001), and a higher preoperative hemoglobin level (OR per 1 g/dL = 0.744, P = 0.004) decreased the risk of transfusion. CONCLUSIONS: In patients with AS undergoing THA, prolonged operative duration, increased estimated intraoperative blood loss, and increased postoperative drainage volume were found to be risk factors for transfusion, whereas a higher BMI, perioperative TXA use, and a higher preoperative hemoglobin level were protective factors. These results may aid in developing a better perioperative management strategy, ultimately reducing the need for transfusion.

A Cross-Sectional Study on Gluteal Muscles in Patients with Ankylosing Spondylitis at Different Stages of Hip Involvement.

Hip involvement in ankylosing spondylitis (AS) is associated with severe functional impairment, and early diagnosis can improve the disease prognosis. We investigated gluteal muscle cross-sectional area (CSA) and radiodensity at different stages of hip involvement and their associations with AS-related clinical and laboratory parameters. This cross-sectional study included 83 patients with AS and 83 age- and sex-matched controls. Patients with AS were divided into three groups according to the Bath Ankylosing Spondylitis Radiology Hip Index system. The CSA and radiodensity of the gluteus maximus, medius, and minimus muscles were measured using computed tomography images. Muscle parameters were compared, and their relationships with clinical and laboratory parameters were evaluated. For the gluteus maximus, patients with AS had a lower CSA than controls, regardless of the degree of hip involvement. For the gluteus medius and minimus, patients with moderate/advanced hip involvement had significantly lower CSA and radiodensity than those with mild to no hip involvement. The severity of hip involvement was negatively associated with muscle parameters. CSA of the gluteus maximus decreased in early-stage hip involvement without any changes in radiographs, while radiodensity decreased in the later stages. Muscle parameters on computed tomography may be a more sensitive indicator than radiographic findings.

CircRNA_0026344 via miR-21 is involved in cigarette smoke-induced autophagy and apoptosis of alveolar epithelial cells in emphysema.

Cigarette smoke (CS), a main source of indoor air pollution, is a primary risk factor for emphysema, and aberrant cellular autophagy is related to the pathogenesis of emphysema. Circular RNAs (circRNAs) affect the expression of mRNAs via acting as microRNA (miRNA) sponges, but their role in emphysema progression is not established. In the present investigation, CS, acting on alveolar epithelial cells, caused higher levels of miR-21, p-ERK, and cleaved-caspase 3 and led to lower levels of circRNA_0026344 and PTEN, which induced autophagy and apoptosis. miR-21 suppressed the expression of PTEN, which was involved in the regulation of autophagy and apoptosis. Further, in alveolar epithelial cells, overexpression of circRNA_0026344 blocked cigarette smoke extract (CSE)-induced autophagy and apoptosis, but this blockage was reversed by upregulation of miR-21 with a mimic. These results demonstrated that, in alveolar epithelial cells, CS decreases circRNA_0026344 levels, which sponge miR-21 to inhibit the miR-21 target, PTEN, which, in turn, activates ERK and thereby promotes autophagy and apoptosis, leading to emphysema. Thus, for emphysema, circRNA_0026344 regulates the PTEN/ERK axis by sponging miR-21, which is associated with the CS-induced autophagy and apoptosis of alveolar epithelial cells. In sum, the present investigation identifies a novel mechanism for CS-induced emphysema and provides information useful for the diagnosis and treatment of CS-induced emphysema.

Development and validation of a DNA damage repair-related gene-based prediction model for the prognosis of lung adenocarcinoma.

Background: Lung cancer is the leading cause of morbidity and mortality among all cancer types, with lung adenocarcinoma (LUAD) being the most prevalent subtype. DNA damage repair (DDR)-related genes are closely associated with cancer progression and treatment, with emerging evidence highlighting their correlation with tumor development. However, the relationship between LUAD prognosis and DDR-related genes remains unclear. Methods: RNA sequencing (RNA-seq) data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. The GSE31210 dataset, utilized for external validation, was retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed DDR genes were identified, and a DDR-related prognostic model was established and validated using Kaplan-Meier (KM) survival analysis, time-dependent receiver operating characteristic (ROC) curves, gene set enrichment analysis (GSEA), tumor mutational burden (TMB) analysis, and immune cell infiltration. A P value of less than 0.05 was considered statistically significant. Results: A total of 514 patients with LUAD from TCGA database were divided into distinct subtypes to characterize the diversity within the DDR pathway. DDR-activated and DDR-suppressed subgroups showed distinct clinical characteristics, molecular characteristics, and immune profiles. Nine genes were identified as hub DDR-related genes, including CASP14, DKK1, ECT2, FLNC, HMMR, IGFBP1, KRT6A, TYMS, and FCER2. By using the expression levels of these selected genes, the corresponding risk scores for each sample was predicted. In the training group, KM survival analysis revealed that the high-risk group exhibited significantly diminished overall survival (OS) [hazard ratio (HR) =3.341, P=1.38e-08]. The corresponding area under the curve (AUC) values for the 1-year follow-up periods was 0.767, respectively. Upon validation in the external cohort, patients with higher risk scores manifested significantly reduced OS (HR =2.372, P=1.87e-03). The AUC values of the ROC curves for the 1-year OS in the validation cohort was 0.87, respectively. Moreover, advanced DDR risk score was correlated with increased TMB scores, a heightened frequency of TP53 mutations, an increased abundance of cancer-testicular antigens (CTAs), and a lower tumor immune dysfunction and exclusion (TIDE) score in patients with LUAD (P<0.05). Conclusions: A nine-gene risk signature associated with DDR in LUAD was effectively developed, demonstrating its potential as a robust and reliable classification tool for clinical practice. This model exhibited the capability to accurately predict the prognosis and survival outcomes of LUAD patients.

High expression of glycolysis-related PGM2 gene in relation to poor prognosis and deficient immune cells infiltration in lung adenocarcinoma: a study based on bioinformatics analysis.

Background: Lung adenocarcinoma (LUAD) is the most important subtype of lung cancer and usually metastasizes. Patients with LUAD usually had a poor prognosis. Identifying viable molecular markers for diagnostic and prognostic prediction among individuals with LUAD is critical for the future management of this disease. This study aimed to determine and verify a correlation between the glycolysis-related phosphoglucomutase 2 (PGM2) gene and dissatisfactory results and deficient infiltration of immune cells in LUAD. Methods: The expression of PGM2 in LUAD and adjoining normal tissues was screened from The Cancer Genome Atlas (TCGA) data and human protein atlas (HPA), and validatied by quantative reverse transcription polymerase chain reaction (qRT-PCR). We examined the correlation between PGM2 expression and clinicopathologic characteristics (including pathological stage, gender, M stage, smoker, age, N stage, race, and number pack years smoked) by multivariable approaches and Kaplan-Meier survival curves. The proteins network with PGM2 was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The correlation between PGM2 expression and infiltration of immune cells, along with the corresponding gene marker sets, was investigated through the Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor Immune Estimation Resource (TIMER) databases. We evaluated the possible correlation between PGM2 expression and progression-free interval (PFI), disease-specific survival (DSS), and overall survival (OS) in LUAD patients. Results: Expression of PGM2 was up-regulated in LUAD tissues (P=0.003). According to the multivariate logistic regression analysis, the elevated expression level of PGM2 exhibited a remarkable correlation with advanced tumor-node-metastasis (TNM) stage, high-grade malignancy, and primary therapeutic outcome . Overexpression of PGM2 was shown to be correlated with an unfavorable prognosis including OS (P=0.004, HR =1.54), DSS (P=0.003, HR =1.77), and PFI (P=0.003, HR =1.5) in LUAD. The proteins PGM1 and UGP2 were shown to have a significant correlation with PGM2. Additionally, PGM2 was associated with the lack of infiltrating immune cells as well as their associated gene marker sets in LUAD. Conclusions: Overexpression of PGM2 was shown to be associated with the progression and an unfavorable prognosis of LUAD, as well as with inefficient immune cell infiltration. PGM2 was expected to be a potential biological marker for predicting the prognosis of patients with LUAD.

Which serum markers predict the success of reimplantation after periprosthetic joint infection?

PURPOSE: In clinical practice, serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels are routinely used to screen for periprosthetic joint infection (PJI), but the effectiveness of predicting the success of reimplantation is variable. This study aimed to evaluate the diagnostic effectiveness of serum CRP, ESR, plasma D-dimer, and fibrinogen values in groups achieving treatment success or failure for PJI. METHODS: A total of 119 PJI cases between January 2012 and January 2017 were identified and included in this study. The most recent serum CRP, ESR, plasma D-dimer, and fibrinogen values obtained prior to performing second-stage revision or spacer exchange were collected for analysis. Treatment failure was defined as having been unable to undergo reimplantation due to clinically persistent infection or reinfection after reimplantation. RESULTS: All these tests showed significantly lower values in the treatment success group than in the treatment failure group. The optimal cutoff serum CRP, ESR, plasma D-dimer, and fibrinogen levels for predicting the success of reimplantation were 9.4 mg/L, 29 mm/h, 1740 ng/mL, and 365.6 mg/dL, respectively. All tests had the same sensitivity (72.7%) except for ESR (63.6%), while their specificities were 92.6%, 88.0%, 72.3%, and 83.2%, respectively. Plasma fibrinogen had the highest AUC value of 0.831 [95% confidence interval (CI), 0.685 to 0.978], followed by serum CRP (0.829) and ESR (0.795); plasma D-dimer had the lowest AUC value of 0.716 (95% CI, 0.573 to 0.859). CONCLUSION: Plasma CRP and fibrinogen are good tests for predicting reimplantation success after two-stage revision procedures for patients with PJI.