Social network and related factors in older people with sensory impairment in the community: Using principal component analysis.

AIM: Older people with sensory impairment are more likely to have smaller and weaker social network due to their reduced ability, which lowers their quality of life. However, there is little research on the social network in older people with sensory impairment, especially the related factors. The aim of the study was to explore the related factors of social network and to provide evidence for the improvement of social network to promote successful aging in older people with sensory impairment. METHODS: A cross-sectional study was conducted among 374 participants for hearing and vision assessment and questionnaire survey in a community, Beijing. Data were collected and analyzed by principal component analysis (PCA) and multiple logistic regression using IBM SPSS 25.0 software. RESULTS: PCA showed that there were six risk factors whose eigenvalues >1 were extracted, with a total variance of 56.555%. Multiple logistic regression analysis of principal component indicated that five factors including physical health factor, social interaction factor, psychological status factor, lifestyle factor, and family condition factor, were statistically significant (p < 0.05). CONCLUSIONS: The social network of older people with sensory impairment is relatively poor. Physical health factor, social interaction factor, psychological status factor, lifestyle factor, and family condition factor may be related factors. Medical staff should pay attention to physical, psychological and social characteristics of older people, especially with sensory impairment, to carry out necessary measures to improve social network and avoid social isolation.

Discovery of lung adenocarcinoma tumor antigens and ferroptosis subtypes for developing mRNA vaccines.

mRNA vaccines are becoming a feasible alternative for treating cancer. To develop mRNA vaccines against LUAD, potential antigens were identified and LUAD ferroptosis subtypes distinguished for selecting appropriate patients. The genome expression omnibus, cancer genome atlas (TCGA) and FerrDB were used to collect gene expression profiles, clinical information, and the genes involved in ferroptosis, respectively. cBioPortal was used to visualize and compare genetic alterations, GEPIA2 to calculate prognostic factors of the selected antigens, and TIMER to visualize the relationship between potential antigens and tumor immune cell infiltration. Consensus clustering analysis was utilized to identify ferroptosis subtypes and their prognostic value assessed by Log-rank and cox regression tests. The modules of ferroptosis-related gene screening were conducted by weight gene co-expression network analysis. The LUAD ferroptosis landscape was visualized through dimensionality reduction and graph learning. Six tumor antigens had obvious LUAD-mutations, positively correlated with different antigen-presenting cells, and might induce tumor cell ferroptosis. LUAD patients were stratified into three ferroptosis subtypes (FS1, FS2, and FS3) according to diverse molecular, cellular, and clinical characteristics. FS3 showed the highest tumor mutation burden and the most somatic mutations, deemed potential indicators of mRNA vaccine effectiveness. Moreover, different ferroptosis subtypes expressed distinct immune checkpoints and immunogenic cell death modulators. AGPS, NRAS, MTDH, PANX1, NOX4, and PPARD are potentially suitable for mRNA vaccinations against LUAD, specifically in patients with FS3 tumors. This study defines vaccination candidates and establishes a theoretical basis for LUAD mRNA vaccinations.

miR-34c-5p inhibited fibroblast proliferation, differentiation and epithelial-mesenchymal transition in benign airway stenosis via MDMX/p53 pathway.

Benign airway stenosis (BAS) means airway stenosis or obstruction that results from a variety of non-malignant factors, including tuberculosis, trauma, benign tumors, etc. In consideration of the currently limited research on microRNAs in BAS, this study aimed to explore the role and mechanism of miR-34c-5p in BAS. The expression of miR-34c-5p in BAS granulation tissues showed a significant down-regulation compared with the normal control group. Moreover, miR-34c-5p mimics suppressed the proliferation and differentiation of human bronchial fibroblasts (HBFs) and the epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBE). Conversely, miR-34c-5p inhibitors aggravated those effects. A dual-luciferase reporter assay confirmed that miR-34c-5p can target MDMX rather than Notch1. The over-expression of MDMX can reverse the inhibiting effect of miR-34c-5p on HBFs proliferation, differentiation and EMT. Furthermore, the expressions of tumor protein (p53) and PTEN were down-regulated following the over-expression of MDMX. In addition, the expressions of PI3K and AKT showed an up-regulation. In conclusion, miR-34c-5p was down-regulated in BAS and may inhibit fibroblast proliferation differentiation and EMT in BAS via the MDMX/p53 signaling axis. These findings expand the understanding of the role of miR-34c-5p and will help develop new treatment strategies for BAS.

Social participation in older people with hearing impairment in Chinese community: A latent profile analysis.

OBJECTIVES: Hearing impairment may lead to increased communication difficulties for older people, making their social participation less optimistic. However, there is little research on the social participation of older people with hearing impairment, especially based on the characteristics of their social participation. This study aimed to identify different social participation profiles in older people with hearing impairment and to explore sociodemographic characteristics, disease-related characteristics and psychosocial factors with different social participation profiles. METHODS: A cross-sectional study of 300 older people with hearing impairment using the sociodemographic questionnaire, the Impact on Participation and Autonomy Questionnaire, the Lubben Social Network Scale-6, Medical Outcomes Study Social Support Survey and Geriatric Depression Scale-15 from May to August 2023 in a community of Beijing, China. Latent profile analysis was used to analyse the latent profiles of social participation in elderly with hearing impairment. Multiple logistic regression was used to explore the predictors of different profiles. RESULTS: The social participation of older people with hearing impairment in the community can be classified into three potential profiles: Profile 1 - high social participation group (76.05 %), Profile 2 - moderate social participation group (17.34 %), Profile 3 - low social participation group (6.61 %). Age, types of chronic diseases, self-reported health, severity of hearing impairment, social network, social support and depression were predictors of different profiles. CONCLUSIONS: Nurses should pay attention to the characteristics, depression, social network and support of older people with different hearing impairment to improve social participation in different profiles. IMPLICATIONS AND RECOMMENDATIONS: This was the first study exploring latent profiles of social participation in older people with hearing impairment. Insights from this study are useful for gerontological nursing to distinguish different profiles and further identify the characteristics of different profiles in older people with hearing impairment by characterizing the level of social participation in the community and better implement interventions according to profiles.

Down-regulation of miR-21-5p by pirfenidone to inhibit fibroblast proliferation in the treatment of acquired tracheal stenosis.

OBJECTIVE: Treatment options for acquired tracheal stenosis (ATS) are limited due to a series of pathophysiological changes including inflammation and cell proliferation. Micro ribonucleic acid-21-5p (miR-21-5p) may promote the excessive proliferation of fibroblasts. However, various types of fibrosis can be prevented with pirfenidone (PFD). Currently, the effect of PFD on miR-21-5p and its biological function has not been clarified. In this study, PFD was evaluated as a potential treatment for ATS by inducing fibroblast proliferation in lipopolysaccharide (LPS)-induced fibroblasts by targeting miR-21-5p. METHODS: For 48 h, 1 g/ml LPS was used to generate fibroblasts in vitro, followed by the separation of cells into four groups: control, PFD, mimic, and mimic + PFD. The Cell Counting Kit-8 (CCK-8) technique was adopted to measure the proliferation of fibroblasts. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) were used to measure the relative expressions of tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), drosophila mothers against decapentaplegic 7 (Smad7) and collagen type I alpha 1(COL1A1) messenger RNA (mRNA) and proteins, respectively. RESULTS: (1) At 0, 24, 48, and 72 h, fibroblast growth was assessed using the CCK-8 method. Compared with the control group, the mimic group showed the highest fibroblast viability, and the PFD group showed the lowest fibroblast viability. However, fibroblast viability increased in the mimic + PFD group but decreased in the mimic one. (2) RT-qPCR and WB showed that the mimic group exhibited a significant up-regulation in the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins but a down-regulation in the relative expression of Smad7 mRNA and protein compared with the control one. In the PFD group, the results were the opposite. Nevertheless, the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins were increased, whereas that of Smad7 mRNA was decreased in the mimic + PFD group. The change was less in the mimic group. CONCLUSION: PFD may have a preventive and curative effect on ATS by inhibiting fibroblast proliferation and the fibrotic process and possibly through down-regulating miR-21-5p and up-regulating Smad7 and its mediated fibrotic and inflammatory responses.

Identification and verification of microtubule associated genes in lung adenocarcinoma.

Associated with high morbidity and mortality, lung adenocarcinoma (LUAD) is lacking in effective prognostic prediction and treatment. As chemotherapy drugs commonly used in clinics, microtubule-targeting agents (MTAs) are limited by high toxicity and drug resistance. This research aimed to analyze the expression profile of microtubule-associated genes (MAGs) in LUAD and explore their therapy efficiency and impact on prognosis. Key MAGs were identified as novel molecular targets for targeting microtubules. The LUAD project in The Cancer Genome Atlas (TCGA) database was used to identify differently expressed MAGs. On the one hand, a microtubule-related prognostic signature was constructed and validated, and its links with clinical characteristics and the immune microenvironment were analyzed. On the other hand, hub MAGs were obtained by a protein-protein interaction (PPI) network. Following the expression of hub MAGs, patients with LUAD were classified into two molecular subtypes. A comparison was made of the differences in half-maximal drug inhibitory concentration (IC50) and tumor mutational burden (TMB) between groups. In addition, the influence of MAGs on the anticancer efficacy of different therapies was explored. MAGs, which were included in both the prognosis signature and hub genes, were considered to have great value in prognosis and targeted therapy. They were identified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 154 differently expressed MAGs were discovered. For one thing, a microtubule-related prognostic signature based on 14 MAGs was created and identified in an external validation cohort. The prognostic signature was used as an independent prognostic factor. For another, 45 hub MAGs were obtained. In accordance with the expression profile of 45 MAGs, patients with LUAD were divided into two subtypes. Distinct differences were observed in TMB and IC50 values of popular chemotherapy and targeted drugs between subtypes. Finally, five genes were included in both the prognosis signature and hub genes, and identified by qRT-PCR. A microtubule-related prognosis signature that can serve as an independent prognostic factor was constructed. Microtubule subtype influenced the efficacy of different treatments and could be used to guide therapy selection. In this research, five key MAGs, including MYB proto-oncogene like 2 (MYBL2), nucleolar and spindle-associated protein 1 (NUSAP1), kinesin family member 4A (KIF4A), KIF15 and KIF20A, were verified and identified. They are promising biomarkers and therapeutic targets in LUAD.

Analysis of clinical characteristics of 617 patients with benign airway stenosis.

Introduction: Benign airway stenosis (BAS), namely airway narrowing caused by a variety of benign lesions, can lead to varying degrees of breathing difficulties and even death due to asphyxia. This study aimed to elucidate the clinical characteristics of BAS, including etiology, treatment and pathology, by analyzing the clinical data of BAS patients. Methods: A retrospective analysis was conducted using the clinical data of 617 BAS cases from January 2017 to December 2022. The pathological characteristics of the tissues were assessed by hematoxylin-eosin (H&E) and Masson's staining. Besides, protein expression levels were determined by immunohistochemistry (IHC). Results: A total of 617 patients were included (333 females [53.97%] and 284 males [46.03%]), with an average age of 48.93 ± 18.30 (range 14-87). Tuberculosis (n = 306, 49.59%) and trauma (n = 179, 29.02%) were the two leading etiologies of BAS, followed by airway foreign bodies (FB, n = 74, 11.99%), external compression (n = 25, 4.05%) and other etiologies (n = 33, 5.35%). Among 306 tuberculous tracheobronchial stenosis (TBTS) cases, most were females (n = 215, 70.26%), and TBTS mainly occurred in the left main bronchus (n = 97, 31.70%), followed by the right middle bronchus (n = 70 cases, 22.88%). The majority of TBTS patients (n = 259, 84.64%) were treated by interventional therapy. The condition of 179 BAS patients was ascribed to trauma, such as tracheal intubation (n = 92, 51.40%), tracheotomy (n = 69, 38.56%), injury (n = 15, 8.38%) and surgery (n = 3, 1.68%), which mostly took place in the trachea (n = 173, 96.65%). TAS patients mainly received interventional therapy (n = 168, 93.85%) and stent implantation (n = 47, 26.26%). The granulation tissues of BAS primarily featured inflammation, proliferation and fibrosis. IHC indicated the up-regulated expressions of transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), collagen type I protein (COL-I) and vimentin, and the down-regulated expression of E-cadherin, which indicated fibrosis and epithelial-mesenchymal transition (EMT). Conclusion: Tuberculosis was the main etiology, and trauma was the secondary etiology. The granulation tissues of BAS were characterized by inflammation, fibrosis and probably EMT. Comprehensive interventional therapy is an effective method of treating BAS.

In vivo hypoglycemic effects of bisphenol F exposure in high-fat diet mice.

Bisphenol F (BPF) is a widely used bisphenol A (BPA) substitute plastic additive that has attracted increasing public concerns due to its potential toxic effects on animal and human health. Although previous studies have indicated that BPF might have harmful effects on metabolic homeostasis, the systematic effects of BPF on glucose disorders remain controversial. In this study, mice fed a normal chow diet (ND) and high-fat diet (HFD) were administered BPF at a dose of 100 µg/kg of body weight, and glucose metabolism was monitored after both short- and long-term treatment. Little change in glucose metabolism was observed in BPF-treated ND mice, but improved glucose metabolism was observed in BPF-treated HFD mice. Consistently, BPF treatment led to increased insulin signalling in the skeletal muscle of HFD mice. Additionally, liver metabolite levels also revealed increased carbohydrate digestion and improved TCA cycle progression in BPF-treated HFD mice. Our results demonstrate that sustained BPF exposure at an environmentally relevant dosage may substantially improve glucose metabolism and enhance insulin sensitivity in mice fed a high-fat diet.

Differential expression of miRNAs revealed by small RNA sequencing in traumatic tracheal stenosis.

Introduction: Traumatic tracheal stenosis (TTS) is a major cause of complex difficult airways, without clinically definitive efficacious drugs available. The aim of this study was to provide a general view of interactions between micro and messenger ribonucleic acids (miRNAs and mRNAs) and many potential mechanisms in TTS via small RNA sequencing. Methods: In this study, the identification of miRNAs was completed using small RNA sequencing and samples from four TTS patients and four normal control cases. By using bioinformatics tools, such as miRanda and RNAhybrid, for identifying the candidate target genes of miRNAs with differential expression in each sample, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were employed for enriching the predicted target genes of miRNAs with differential expression based on the correspondence between miRNAs and their target genes. We detected the expression of the candidate miRNAs using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Twenty-four miRNAs with significant differential expression were identified, including 13 upregulated and 11 downregulated ones. Bioinformation technology was adopted to predict 2,496 target genes. These miRNA-target genes were shown to be primarily enriched in cells and organelles with catalytic activity and binding function, such as binding proteins, small molecules, and nucleotides. Finally, they were observed to process into TTS through the intercellular and signal regulation of related inflammatory signaling and fibrosis signaling pathways. QRT-PCR confirmed the upregulation of miR21-5p and miR214-3p and the downregulation of miR141-3p and miR29b-3p, which was expected to become a high-specific miRNA for TTS. Conclusion: Among all the miRNAs detected, 24 miRNAs demonstrated differential expression between the TTS and normal control groups. A total of 2,496 target genes were predicted by bioinformation technology and enriched in inflammatory and fibrotic signaling pathways. These results provide new ideas for further studies and the selection of targets for TTS in the future.

The miR-3648/FRAT1-FRAT2/c-Myc negative feedback loop modulates the metastasis and invasion of gastric cancer cells.

Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the molecular mechanisms underlying miR-3648 progression and metastasis in gastric cancer (GC) remain unclear. miR-3648 expression is downregulated and its ectopic expression in GC cells significantly suppressed cell proliferation and metastasis. Mechanistic analyses indicated that miR-3648 directly targets FRAT1 or FRAT2 and inhibits FRAT1- or FRAT2-mediated invasion and motility in vitro and in vivo. Moreover, FRAT1 physically interacted with FRAT2. Furthermore, FRAT1 overexpression promoted GC cell invasion, whereas siRNA-mediated repression of FRAT2 in FRAT1-overexpressing GC cells reversed its invasive potential. Besides, miR-3648 inactivated the Wnt/ß-catenin signalling pathway by downregulating FRAT1 and FRAT2 in GC. Interestingly, c-Myc, a downstream effector of Wnt/ß-catenin signalling, was also downregulated by miR-3648 overexpression. In turn, c-Myc negatively regulated miR-3648 expression by binding to the miR-3648 promoter. In addition, miR-3648 expression levels were negatively correlated with c-Myc, FRAT1, and FRAT2 expression in fresh gastric samples. Our studies suggest that miR-3648 acts as a tumour-suppressive miRNA and that the miR-3648/FRAT1-FRAT2/c-Myc negative feedback loop could be a critical regulator of GC progression.

Prognostic Risk Signature and Comprehensive Analyses of Endoplasmic Reticulum Stress-Related Genes in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the main pathological subtype of non-small-cell lung cancer. Endoplasmic reticulum stress (ERS) has been found to be involved in multiple tumor-related biological processes. At present, a comprehensive analysis of ERS-related genes in LUAD is still lacking. A total of 1034 samples from TCGA and GEO were used to screen differentially expressed genes. Further, Random Forest algorithm was utilized to screen characteristic genes related to prognosis. Then, LASSO Cox regression was used to construct a prognostic signature. Taking the median of signature score as the threshold, patients were separated into high-risk (HR) group and low-risk (LR) group. Tumor mutation burden (TMB), immune cell infiltration, cancer stem cell infiltration, expression of HLA, and immune checkpoints of the two risk groups were analyzed. TIDE score was used to evaluate the response of the two risk groups to immunotherapy. Finally, the gene expression was verified in clinical tissues with RT-qPCR. An eight-gene signature (ADRB2, AGER, CDKN3, GJB2, SFTPC, SLC2A1, SLC6A4, and SSR4) was constructed. TMB and cancer stem cell infiltration were higher in the HR group than the LR group. TIDE score and expression level of HLA were higher in the LR group than the HR group. Expression level of immune checkpoints, including CD28, CD27, IDO2, and others, were higher in the LR group. Multiple drugs approved by FAD, targeting ERS-related genes, were available for the treatment of LUAD. In summary, we established a stable prognostic model based on ERS-related genes to help the classification of LUAD patients and looked for new treatment strategies from aspects of immunity, tumor mutation, and tumor stem cell infiltration.

Disruption of the CCDC43-FHL1 interaction triggers apoptosis in gastric cancer cells.

The coiled-coil domain-containing protein 43 (CCDC43) is essential to promote gastric cancer (GC) proliferation and invasion, while four and a half LIM domains 1 (FHL1) involves GC cells apoptosis. We attempted to address inter-relationship between CCDC43 and FHL1 in modulating GC cells growth and apoptosis. Levels of protein expression were assessed by western blot, immunofluorescence. Using EdU, plate colony formation, Matrigel invasion and animal models, we evaluated the function in vitro and in vivo. Apoptosis was evaluated by flow cytometry and Hoechst 33258 staining. Reciprocal co-immunoprecipitation (co-IP) analyses indicated that CCDC43 physically interacted with FHL1. The expression of CCDC43 was negatively correlated with FHL1. Moreover, up-regulation of CCDC43 resulted in FHL1 level decline, and the reverse is also true. CCDC43 expressed jointly with FHL1 group significantly decreases the ability of the growth, metastasis and invasion of GC cells compared with that of the CCDC43 group. Furthermore, siRNA-mediated repression of CCDC43 results in dissociation from FHL1 and causes suppression of GC cell proliferation and metastasis. CCDC43 repression mediates the stability of FHL1 protein. In addition, CCDC43 interacts with FHL1. Knockdown of CCDC43 plus FHL1 overexpression inhibits proliferation and migration and induces apoptosis of GC cells in vitro and vivo.

Talaromyces Marneffei Infection in Lung Cancer Patients with Positive AIGAs: A Rare Case Report.

BACKGROUND: Talaromyces marneffei is considered to commonly cause infection in individuals with human immunodeficiency virus (HIV) infection. However, the epidemiology of T. marneffei has changed, and an increasing number of HIV-negative but immunodeficient patients are infected with T. marneffei. The mechanisms of T. marneffei infection of HIV-negative hosts are complex and diverse. We report 2 cases of HIV-negative lung cancer with T. marneffei infection and positive anti-interferon-gamma autoantibodies (AIGAs) to provide clinical experience. CASE PRESENTATION: We report lung adenocarcinoma combined with T. marneffei infection in HIV-negative patients, and their AIGAs were measured. Both patients were male with a family history of cancer and presented with recurrent fever and cough. The patients were negative for HIV antibodies but positive for AIGAs. Chest computed tomography (CT) showed pulmonary nodules, exudative lesions and solid changes. The patients were diagnosed with lung adenocarcinoma and Talaromycosis marneffei (TSM) by pathological examination and tissue culture. Patient 1 received only antifungal treatment, refused antitumor treatment and died in February 2019, and Patient 2 unfortunately died in April 2019 after antifungal and antitumor treatments. CONCLUSION: An increasing number of HIV-negative but immunodeficient patients are infected with T. marneffei. The 2 patients in this report had lung cancer and positive AIGAs, causing immunodeficiencies, but the mechanism of T. marneffei infection in such patients is complex. Clinically, we should consider a comprehensive immunological examination to avoid the omission of other immunodeficiencies. We recommend routine testing for AIGA levels in HIV-negative marneffei patients. It is difficult to distinguish between lung cancer and disseminated TSM due to similar clinical characteristics and imaging, and multiple biopsies and cultures of diseased tissue are necessary. Early antifungal treatment and standard antitumor treatment can achieve satisfactory curative effects when a patient has both diseases.

Vorinostat triggers miR-769-5p/3p-mediated suppression of proliferation and induces apoptosis via the STAT3-IGF1R-HDAC3 complex in human gastric cancer.

Previous reports have shown that histone deacetylase inhibitors (HDACi) can alter miRNA expression in a range of cancers. Both the 5p-arm and 3p-arm of mature miRNAs can be expressed from the same precursor and involved in cancer progress. Nevertheless, the detailed mechanism by which vorinostat (SAHA), a HDACi, triggers miR-769-5p/miR-769-3p-mediated suppression of proliferation and induces apoptosis in gastric cancer (GC) cells remains elusive. Here, we showed that the miRNA-seq analysis of GC cells treated with SAHA identified seven differentially expressed miRNAs with both strands of the miRNA duplex. miR-769-5p/miR-769-3p expression was downregulated in GC tissues compared with normal tissues. Functionally, high expression of miR-769-5p/miR-769-3p blocked the malignant abilities of GC cells. Mechanistically, miR-769-5p/miR-769-3p targeted IGF1R and IGF1R overexpression rescued the effects of miR-769-5p/miR-769-3p on GC cells growth and metastasis. Moreover, STAT3 bound to the promoter of miR-769. Furthermore, miR-769-5p/miR-769-3p expression was negatively regulated by the STAT3-IGF1R-HDAC3 complex. Besides, miR-769-5p/miR-769-3p synergized with SAHA to promote GC cells apoptosis. Our studies suggest that miR-769-5p/miR-769-3p acts as a tumor suppressor by the STAT3-IGF1R-HDAC3 complex. Moreover, SAHA triggers miR-769-5p/miR-769-3p-mediated inhibition of proliferation and induces apoptosis in GC cells.

Construction and validation of risk prediction model for deep vein thrombosis in acute exacerbations of chronic obstructive pulmonary disease based on serum angiopoietin 2 levels.

BACKGROUND: This study aims to establish a predictive risk model for deep vein thrombosis (DVT) in patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) based on serum angiopoietin 2 (Ang-2) levels. METHODS: The research sample consisted of 650 patients with AECOPD admitted to the First Affiliated Hospital of Chengdu Medical College from January 2019 to January 2021, who were subsequently divided into a modeling group and a verification group. A univariate analysis was performed on the identified risk factors for DVT in AECOPD, and the significant factors were then incorporated into a multivariate logistic regression model to screen for the independent predictors of DVT. A nomogram was constructed, and a receiver operating characteristic curve (ROC), Hosmer-Lemeshow test, decision curve, and clinical impact curve in the modeling and validation cohort were used to analyze the discrimination power, calibration, and clinical validity of the predictive risk nomogram model of AECOPD with comorbid DVT. RESULTS: Univariate and multivariate logistic regression analyses showed that lower limb edema, BMI, diabetes, respiratory failure, D-dimer, and serum Ang-2 were risk factors for DVT in AECOPD. A nomogram model for predicting AECOPD with comorbid DVT was successfully established. The AUC values for the modeling group and the verification group were 0.844 (95% CI: 0.808-0.932) and 0.755 (95% CI: 0.679-0.861), respectively. According to the Hosmer-Lemeshow test, the P values of the nomogram in the modeling group and the verification group were 0.124 and 0.086, respectively. The decision curve and clinical impact curve suggested that most patients can benefit from this prediction model, and the predicted probability of the model was essentially the same as the actual clinical probability of DVT. CONCLUSIONS: The predictive risk nomogram model of AECOPD with comorbid DVT based on serum Ang-2 levels has good discrimination power, calibration, and clinical influence. The model is a good fit and has a high predictive value, which helps clinicians identify AECOPD patients at high risk of DTV and formulate corresponding prevention and treatment measures.

Protective effects of different anti­inflammatory drugs on tracheal stenosis following injury and potential mechanisms.

Tracheal stenosis following injury cannot be effectively treated. The current study compared the protective effects of different anti­inflammatory drugs on tracheal stenosis and investigated their possible mechanisms. Rabbit tracheal stenosis models following injury were constructed and confirmed using hematoxylin and eosin (H&E) staining. A total of 30 rabbits were divided into the control (CON), penicillin (PEN), erythromycin (ERY), budesonide (BUD) and PEN + ERY + BUD groups (n=6). Stenotic tracheal tissue, serum and bronchoalveolar lavage fluid (BALF) were collected 10 days after continuous treatment. Pathological changes in the tracheas were observed by H&E staining. Histone deacetylase 2 (HDAC2) expression in tracheal tissues was detected by immunofluorescence. Immunohistochemistry was performed to detect collagen I (Col­I) and collagen III (Col­III) levels in tracheal tissues. Transforming growth factor ß1 (TGF­ß1), vascular endothelial growth factor (VEGF) and interleukin 8 (IL­8) levels in serum and BALF samples were determined using ELISA kits. Western blotting detected HDAC2, IL­8, TGF­ß1 and VEGF levels in tracheal tissues. H&E staining demonstrated that tracheal epithelial hyperplasia and fibroblast proliferation in the ERY and PEN + ERY + BUD groups markedly improved compared with the CON group. Furthermore, in tracheal tissues, HDAC2 expression was significantly increased and IL­8, TGF­ß1, VEGF, Col­I and Col­III levels were significantly decreased in the ERY and PEN + ERY + BUD groups compared with the CON group. Additionally, the results for the PEN + ERY + BUD were more significant compared with the ERY group. In serum and BALF samples, IL­8, TGF­ß1 and VEGF levels in the ERY and PEN + ERY + BUD groups were significantly lower compared with the CON group, with the results of the PEN + ERY + BUD group being more significant compared with the ERY group. There were no significant differences between the PEN, BUD and CON groups. ERY inhibited tracheal granulation tissue proliferation and improved tracheal stenosis following injury and synergistic effects with PEN and BUD further enhanced these protective effects. The mechanism may involve HDAC2 upregulation and inhibition of local airway and systemic inflammatory responses.

Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-ß1/Smad and Akt/mTOR pathways.

Traumatic tracheal stenosis (TS) is a serious respiratory disease characterized by hyperplasia of airway granulation. Plumbagin (PLB) is a natural naphthoquinone component with anti-fibrotic properties. This research aimed to explore the roles of PLB in alleviating TS and the underlying mechanisms. For in vitro studies, lung fibroblasts (IMR-90 cells), with/without PLB treatment or TGF-ß1 induction, were used. The viability and proliferation of IMR-90 cells were examined by CCK-8 and EdU incorporation assays. The differentiation of IMR-90 cells was assessed by detecting the mRNA and protein expression levels of collagen (COL)-1 and alpha-smooth muscle actin (α-SMA). Besides, immunofluorescence assay was conducted to evaluate the localization of α-SMA in TGF-ß1-induced IMR-90 cells. Moreover, the combination of PLB with/without TßRI (SB-431,542), PI3K/Akt (Ly294002) or mTOR (rapamycin) inhibitor was pretreated on IMR-90 cells after TGF-ß1 induction. For in vivo studies, a rat model of TS was established. The pathological features and severity of TS were determined by hematoxylin and eosin staining. The protein levels of TGF-ß1/Smad and Akt/mTOR pathways were detected for both in vitro and in vivo models. PLB effectively inhibited the proliferation and differentiation of TGF-ß1-induced IMR-90 cells, and suppressed TGF-ß1/Smad and Akt/mTOR signaling pathways both in vivo and in vitro. Furthermore, PLB reduced the degree of TS in rats. Taken together, our results indicate that PLB regulates lung fibroblast activity and attenuates TS in rats by inhibiting TGF-ß1/Smad and Akt/mTOR signaling pathways. In conclusion, this study implies that PLB may serve as a promising therapeutic compound for TS.

Quantized doping of CdS quantum dots with twelve gold atoms.

Through a bottom-up strategy, CdS quantum dots (QDs) doped with 12 gold atoms in each nanocrystal (NC) were prepared by cation exchange reactions. The (Au12) dopants inside the CdS matrix were directly observed using Cs-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) images and quantitatively confirmed using the inductively coupled plasma atomic emission spectroscopy (ICP-AES) data. With a photoluminescence quantum yield (PLQY) of 37.5%, the as-prepared (Au12)@CdS QDs emitted light at 635 nm. Due to the injection of excited electrons from the lowest unoccupied molecular orbital (LUMO) of dopants to the conduction band (CB) of CdS, multiple fine peaks were observed in the photoluminescence excitation (PLE) spectra. By using clusters as starting materials, we demonstrate a universal approach for the precise tailoring of dopants and provide a pathway for band energy engineering of doped QDs.