BACKGROUND:Pulmonary hypertension (PH) is a progressive disorder with high pulmonary arterial pressure, causing right ventricular dysfunction. Understanding PH's molecular basis is vital for therapy development, but research on lactylation's role in PH is limited and needs more investigation. METHODS:We integrated bulk RNA-seq datasets (GSE113439, GSE186996) and single-cell RNA-seq data (GSE210248) from PH patients and controls Differential expression analysis identified lactylation-associated hub genes. Functional enrichment (GO/KEGG), immune infiltration, and cell-cell communication analyses were performed. In vitro validation included RT-PCR and western blot on hypoxic pulmonary artery smooth muscle cells (PASMCs). RESULTS:We identified lymphocyte cytosolic protein 1 (LCP1) as a core lactylation-related hub gene, significantly upregulated in PH and validated in human/rat models. Single-cell profiling revealed elevated lactylation levels in vascular smooth muscle cells (VSMCs), T lymphocytes, and monocytes/macrophages within PH tissues. Cell communication analysis implicated TWEAK signaling from monocytes/macrophages to VSMCs as a driver of vascular remodeling. Metabolic pathways (e.g., glycolysis, bile acid metabolism) correlated strongly with lactylation activity. In vitro, hypoxia-induced LCP1 overexpression in PASMCs confirmed bioinformatic findings. CONCLUSION:We analyzed lactylation-related genes in PH, identifying LCP1 as a key diagnostic marker, and described immune cell lactylation in PH patients, offering insights for future research.

Silica-induced pulmonary fibrosis is a debilitating condition with limited therapeutic options. Allicin, a bioactive compound derived from garlic, has shown potential anti-inflammatory and antifibrotic properties. However, its role in silica-induced pulmonary fibrosis remains unexplored. Human lung epithelial cells (BEAS-2B) and alveolar epithelial cells (A549) were exposed to silica particles, followed by allicin treatment. In vivo experiments, a murine model of silica-induced pulmonary fibrosis was established, and lentiviral tracheal instillation was employed to validate the impact of Serpinb2 knockdown on fibrotic progression. Fibrosis and ferroptosis markers, including GSH/GSSG, MDA and hydroxyproline content, were assessed. Molecular mechanisms were evaluated using Western blot, RT-PCR, and Immunofluorescence to analyze Serpinb2 expression and NF-κB pathway activation. Allicin can alleviate ferroptosis and pulmonary fibrosis induced by silica. In addition, Serpinb2 is upregulated under the induction of silicon dioxide. Inhibiting Serpinb2 can alleviate ferroptosis and pulmonary fibrosis induced by silicon dioxide. Meanwhile, the addition of allicin can inhibit Serpinb2 and thereby exert the same effect. NF-κB functions as a downstream pathway of Serpinb2. The addition of allicin can inhibit Serpinb2 and thereby suppress the NF-κB pathway, thereby exerting its inhibitory effect on ferroptosis and pulmonary fibrosis. This study demonstrates that allicin attenuates silica-induced pulmonary fibrosis by modulating Serpinb2/NF-κB pathway via inhibiting ferroptosis. These results highlight the therapeutic potential of allicin in treating pulmonary fibrosis and provide a novel mechanistic insight into its antifibrotic effects.

Pulmonary aspergillosis (PA) encompasses a heterogeneous spectrum of fungal diseases, including invasive, chronic, and allergic forms. The hospital burden of pulmonary aspergillosis during the COVID-19 era remains incompletely understood. We conducted a single-center retrospective study of hospitalized patients diagnosed with PA at a tertiary hospital in northern Anhui Province, China, between January 1, 2010, and December 31, 2024. Temporal trends, clinical characteristics, microbiological findings, diagnostic indicators, treatment timing, and short-term clinical outcomes were analyzed. Patients were compared between the pre-COVID-19 period and the COVID-19 era. A total of 378 hospitalized PA cases were included. The annual number of PA cases increased over the study period, with a more pronounced increase during the COVID-19 era than during the pre-COVID-19 period, corresponding to an average annual increase of 35.2 cases versus 1.49 cases, respectively. Aspergillus fumigatus was the predominant identified species, accounting for 54.87

In this study, we selected Acinetobacter baumannii Ab2897, a strain from our laboratory, as the host, while the lytic bacteriophage vB_AbaP_IME546 was isolated from untreated hospital sewage. We examined the phage's biological characteristics and found that its latent period was under 5 min, with complete lysis of the bacteria occurring within 60 min. The plaques formed by the bacteriophage showed a halo, indicating the presence of an antibacterial protein. Consequently, this phage underwent next-generation sequencing. A BLAST analysis of the assembled genome sequence indicated that vB_AbaP_IME546 is a novel bacteriophage. After carrying out RAST annotation, it was proposed that the tail fiber protein of the bacteriophage might possess depolymerase activity. To further explore this, the ORF49 gene encoding the tail fiber protein was cloned and expressed. The resulting protein, Dp49, was successfully generated. When the protein was applied to a double-layer plate assay, a transparent halo formed in the area surrounding the bacterial growth. This finding confirms that the IME546 phage exhibits depolymerase activity during the lysis of Ab2897.

Biomimetics is an interdisciplinary field that involves studying the structures, functions, principles, and behaviors of biological systems to draw inspiration and apply this knowledge to technological innovation and engineering design, thereby addressing complex challenges. ​​Biomimetic nanomedicine​​ represents a specific application of biomimetics within the realm of nanomedicine, where biological components are mimicked to construct sophisticated nanodrug delivery systems. These biomimetic nanosystems exhibit multiple unique advantages, including ​​targeted delivery to cells within the tumor microenvironment (TME)​​, ​​prolonged in vivo circulation time​​, ​​enhanced antigen/adjuvant loading capacity​​, and ​​high biocompatibility​​. These properties collectively ​​enhance the efficacy of chemotherapy, radiotherapy, immunotherapy, and photodynamic therapy (PDT)​​ by improving tumor-specific targeting and reducing off-target toxicity, thereby establishing biomimetic nanomedicines as ​​a promising platform for reprogramming the TME​​. This review highlights the ​​categorization​​, ​​design principles​​, and ​​manufacturing strategies​​ of biomimetic nanodrugs, providing a ​​systematic review​​ of the interplay between the TME and ​​biomimetic nanomedicines​​, and elucidating how their interaction potentiates tumor-killing efficacy​​. Despite encouraging progress in biomimetic nanomedicines, challenges remain in their clinical translation, including biosafety concerns, scalable manufacturing processes, and optimal drug delivery efficiency. Advances in nanotechnology and precision engineering offer promising avenues for developing personalized biomimetic nanomedicines.

Rationale: Mitophagy plays an important role in pulmonary hypertension, a progressive disease characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). Long intergenic non-protein coding RNA 3047 (LINC03047), as a hypoxia-related lncRNA, is involved in the progression of various diseases. This study aims to elucidate the mechanism by which LINC03047 in hypoxic pulmonary hypertension (HPH). Methods: Dysregulated LINC03047 was identified through lncRNA sequencing. Reactive oxygen species assay, mitochondrial membrane potential assay, immunofluorescence staining, cell proliferation experiment, gain- and loss-of-function experiments were conducted to elucidate its role in mitophagy and proliferation of hypoxia-induced PASMCs and HPH progression. The upstream transcription regulation mechanism of LINC03047 was identified and verified by comprehensive methods, including reverse transcription-polymerase chain reaction, western blotting, luciferase assay, chromatin immunoprecipitation and rescue experiments. RNA pulldown, mass spectrometry, and RNA immunoprecipitation were employed to identify the potential interacting proteins of LINC03047, and further elucidate the regulatory mechanism between LINC03047 and its downstream targets. Furthermore, the HPH rat model and serum samples from PH patients were utilized to assess its in vivo impact and clinical relevance. Results: We observed that LINC03047 was significantly upregulated in hypoxia-induced PASMCs and promoted their mitophagy and proliferation.Mechanistically, signal transducer and activator of transcription 3 (STAT3) specifically interacted with the LINC03047 promoter and promoted the transcription of LINC03047. Furthermore, LINC03047 bound to heterogeneous nuclear ribonucleoprotein F (hnRNPF), altering the nuclear transport of hnRNPF, thereby upregulating the stability of connective tissue growth factor (CTGF) RNA. In vivo, targeting hnRNPF can ameliorate pulmonary vascular remodeling and HPH progression. The assessment of serum STAT3 and CTGF levels in PH patients indicated a strong positive correlation between the two biomarkers. Conclusions: The overexpression of LINC03047, driven by STAT3, facilitates PASMCs mitophagy by enhancing hnRNPF-mediated CTGF mRNA stability, thus promoting PASMCs proliferation and HPH progression. These findings highlight the critical role of LINC03047, providing new insights into the pathogenesis and potential treatment of HPH.

Lactylation is a post-translational modification that can influence the onset and progression of various diseases.However, its role in Idiopathic Pulmonary Fibrosis (IPF) has not been systematically investigated. Single-cell sequencing and bulk RNA sequencing techniques were utilized to assess lactylation levels in IPF patients and health people. The clinical significance of lactylation was explored through survival and correlation analyses. Optimal feature genes of lactylation were identified using correlation analysis, multiple machine learning algorithms, Cox regression analysis and Mendelian randomization. The potential mechanisms of these Optimal feature genes were inferred through pseudotime analysis and gene pathway activity analysis, followed by experimental validation. Cell-cell communication and metabolic assessments were employed to explore the reasons for elevated lactylation levels in IPF, and relevant findings were verified through in vitro cellular experiments. Both single-cell sequencing and bulk RNA sequencing consistently demonstrated elevated lactylation levels in the IPF patients. High lactylation levels were associated with worse lung function and poorer prognosis. Through the integration of five machine learning algorithms, Cox regression analysis and Mendelian randomization, two optimal feature genes IGFBP7 and CCT2 were identified. These optimal feature genes were found to be significantly highly expressed in vascular endothelial cells, and this conclusion was experimentally validated. Pseudotime analysis results combined with RNA interference (RNAi) and wound healing assays demonstrated that both optimal feature genes promoted endothelial-mesenchymal transition (EndMT) in endothelial cells. Through cell-cell communication analysis, we discovered that TGF-β can promote metabolic reprogramming in endothelial cells, leading to increased lactate production and ultimately elevated expression of the optimal feature genes. Lactylation levels are significantly increased in IPF patients. TGF-β can induce metabolic reprogramming in endothelial cells, leading to high expression of IGFBP7 and CCT2, thereby promoting EndMT.

BACKGROUND:This study provides an updated analysis of the global burden of pneumoconiosis from 1990 to 2021, categorizing by etiology (silicosis, asbestosis, coal workers' pneumoconiosis, and other pneumoconioses) using data from the Global Burden of Disease (GBD) Study 2021. METHODS:We extracted data on incidence, prevalence, deaths, and disability-adjusted life years (DALYs) from GBD 2021 for 204 countries and territories. We calculated age-standardized rates (ASRs) and used linear regression to estimate the average annual percentage change (EAPC) in ASRs to quantify trends. Analyses were stratified by age, sex, sociodemographic index (SDI), and geographic region. Pearson correlation was employed to assess the relationship between ASRs and SDI. RESULTS:In 2021, silicosis was the most burdensome form, exhibiting the highest ASRs for all measures. From 1990 to 2021, the global burden of silicosis, coal workers' pneumoconiosis, and other pneumoconioses significantly declined (all EAPCs <0). In contrast, the ASRs of incidence and prevalence for asbestosis increased. The burden demonstrated substantial geographic variation, with men and the elderly being the most affected populations. Correlation analyses indicated a critical role of SDI levels in influencing the burden. CONCLUSION:The global burden of pneumoconiosis remains a significant public health challenge, with notable etiological and geographic disparities. These findings underscore the need for targeted prevention and control strategies tailored to specific regions and populations.

Pseudomonas aeruginosa (P. aeruginosa), a major cause of severe respiratory infections, particularly ventilator-associated pneumonia (VAP), employs various virulence mechanisms that remain incompletely characterized. In this study, we report that PA0833, an OmpA family outer membrane protein, acts as a novel virulence factor that is involved in the regulation of bacterial pathogenicity. We demonstrate that intranasal administration of recombinant PA0833 alone induces significant pulmonary inflammation in mice, characterized by alveolar disruption, neutrophil infiltration, and elevated pro-inflammatory cytokine levels in BALF, independent of live bacteria. Deletion of PA0833 attenuated virulence, reducing mortality, weight loss, lung inflammation, and tissue damage in P. aeruginosa infected mice, without affecting bacterial growth or colonization. Mechanistically, PA0833 triggered pro-inflammatory cytokine secretion in macrophages via TLR2-dependent activation of the NF-κB pathway, confirmed by TLR2 inhibition and co-immunoprecipitation. Furthermore, PA0833 deletion significantly impaired biofilm formation and reduced extracellular polysaccharide (EPS) content. This defect correlated with downregulation of key genes (mucA, mucB, algB, algD, algU) in the MucA-AlgU EPS biosynthesis pathway. Scanning electron microscopy revealed compromised cell wall integrity in the ΔPA0833 mutant. Collectively, our result indicates that PA0833 contributes to the virulence of P. aeruginosa, and targeting PA0833 offers a promising strategy for novel therapeutics against P. aeruginosa lung infections.

BACKGROUND:Silica-induced pulmonary fibrosis involves epithelial-mesenchymal transition(EMT) and ferroptosis, but the regulatory roles of long non-coding RNAs in these processes remain unclear. This study investigates the role of LINC00324 in ferroptosis and EMT which contribute to silica-induced pulmonary fibrosis. METHODS:A549 and BEAS-2B were exposed to SiO₂ (100 μg/mL, 24 h). Molecular analyses included chromatin immunoprecipitation (ChIP), dual-luciferase reporter assays, RNA immunoprecipitation, and functional rescue experiments. In vivo validation C57BL/6 mice were treated with intratracheal silica instillation (50 mg/kg) and lentiviral-mediated SLC3A2 overexpression (5 × 107 TU), followed by histopathological/biochemical analyses at day 28. RESULTS:Silica exposure transcriptionally suppressed LINC00324 via impaired RBP-J binding to its promoter region. LINC00324 overexpression mitigated silica-induced ferroptosis and EMT, while its knockdown aggravated ferroptosis and EMT. Further studies showed that LINC00324 played a regulatory role in ferroptosis and EMT through SLC3A2. RBP-J, as a transcription factor upstream of LINC00324, regulates ferroptosis and EMT in silica-induced pulmonary fibrosis through SLC3A2. In vivo, SLC3A2 overexpression alleviated silica-induced pulmonary fibrosis. CONCLUSION:Collectively, the RBP-J/LINC00324/SLC3A2 pathway regulates ferroptosis -EMT coupling in silicosis. RBP-J regulates ferroptosis and EMT by binding to the promoter region of LINC00324 and regulating the downstream SLC3A2. Therapeutic targeting of this pathway may combat silica-induced pulmonary fibrosis.

Chronic cough, which affects approximately 10 % of the global population, is recognized as a significant health issue, especially among females. Recent research suggests that chronic cough may be an independent disease rather than merely a symptom of other conditions. This study focuses on the potential role of exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS) in the development of chronic cough, noting that PFAS exposure has been linked to various adverse health outcomes. We aimed to explore the association between PFAS exposure and the risk of chronic cough in the U.S. population, analyzing data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2012 and examining potential sex-based differences. Our findings reveal several factors independently associated with an increased incidence of chronic cough, including elevated levels of serum perfluorobutane sulfonic acid (PFBS) and perfluoroheptanoic acid (PFHP). The multi-pollutant models consistently demonstrated a significant positive correlation between PFAS exposure and a higher risk of chronic cough in adult males, with PFBS and PFHP as the primary contributors. However, due to the cross-sectional design of the NHANES study, further research is necessary to elucidate the precise mechanisms by which PFAS contribute to chronic cough.

Pulmonary hypertension (PH) is a progressive and debilitating vascular disorder characterized by pulmonary vascular remodeling, primarily driven by the excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). In this pathogenic process, mitophagy, a selective form of autophagy, has been identified as playing a pivotal role. Long non-coding RNAs (lncRNAs) are increasingly recognized as significant regulatory elements in various diseases; however, their specific functions in the context of PASMCs mitophagy and proliferation remain largely unexplored. This study aims to investigate the role of a hypoxia-associated lncRNA, long intergenic non-protein coding RNA 3047 (LINC03047), in modulating mitophagy and cellular proliferation in hypoxia-induced PASMCs. Our findings reveal that LINC03047 is significantly upregulated in PASMCs under hypoxic conditions and promotes cell proliferation by activating mitophagy. Mechanistically, we demonstrate that LINC03047, which is transcriptionally regulated by the signal transducer and activator of transcription 3 (STAT3), physically binds to heterogeneous nuclear ribonucleoprotein F (hnRNPF). This interaction inhibits the nuclear translocation of hnRNPF and enhances the stability of connective tissue growth factor (CTGF) mRNA, thereby amplifying its downstream effects. Furthermore, in vivo experiments confirmed that targeted inhibition of hnRNPF effectively mitigates the development of hypoxia-induced PH in model systems. Collectively, these findings elucidate a novel regulatory axis and demonstrate that targeting the STAT3/LINC03047/hnRNPF/CTGF signaling pathway offers a promising therapeutic strategy for the treatment of PH.

OBJECTIVES:According to the data, mutations in EGFR-related genes are the main cause of Non-Small Cell Lung Cancer (NSCLC), necessitating the development of new drug constructs for EGFR-TKIs particularly important. This study aimed to screen potential third-generation EGFR-TKIs to address the emerging drug resistance challenges in NSCLC. METHODS:In this study, virtual screening, molecular dynamics modeling, and bioactivity evaluation were carried out to find a potential EGFR inhibitor that could overcome the L858R/T790M mutation. At first, 12 potential compounds were screened step by step from about 250,000 structures by virtual screening. These 12 compounds were subjected to MTT antitumor activity evaluation and kinase inhibition assay to select compounds with strong antiproliferative effects on cancer cells. Then, the preferred compounds were subjected to time-dependent assay, scratch assay, AO staining assay, and hemolysis assay. Finally, the preferred compound was subjected to molecular docking and molecular dynamics simulation with 5HG7 protein. RESULT:The IC50 of T22306 on H1975 cells was 9.17 μM. In further kinase evaluation, the kinase inhibition of EGFRL858R/T790M was 69.17%. In addition, time-dependent experiments and scratch and AO staining assays confirmed the potential of T22306 as an EGFR-TKI inhibitor, while hemolysis assays demonstrated no significant toxicity. Finally, molecular docking revealed the formation of critical hydrogen bonds between T22306 and LEU- 718. Furthermore, molecular dynamics simulations showed that the T22306-5HG7 complex has a low binding energy (-117.73 ± 18.69 kJ/mol), thus suggesting that T22306 binds tightly to the target protein 5HG7. CONCLUSION:In this study, we rapidly screened potential compounds against NSCLC with the help of virtual screening technology. Further in vitro experiments demonstrated that T22306 successfully overcame the L858R/T790M mutation and could be a potential epidermal growth factor receptor inhibitor.

BACKGROUND:Pulmonary hypertension (PH) is a severe disorder, with hypoxic PH (HPH) representing a major subtype characterized by elevated pulmonary artery pressure due to chronic hypoxia. Long noncoding RNAs are implicated in various cellular processes, but their role in mitophagy regulation within pulmonary artery smooth muscle cells remains unclear. This study aims to investigate the role of long noncoding RNA XLOC_010588 (XLOC_010588) in modulating mitophagy and HPH pathogenesis. METHODS:We examined the interaction between XLOC_010588 and BAG2 (BCL2-associated athanogene 2), a regulator of PINK1 (PTEN-induced putative kinase 1) stability, using molecular and cellular assays. The role of XLOC_010588 in BAG2-mediated PINK1 stabilization and mitophagy activation was assessed in hypoxic pulmonary artery smooth muscle cells. Additionally, the transcriptional regulation of XLOC_010588 by SP1 (specificity protein 1) was investigated. Clinical samples from patients with HPH were analyzed for SP1/BAG2/PINK1 expression, and in vivo experiments were conducted in HPH rats with BAG2 knockdown to evaluate its therapeutic potential. RESULTS:XLOC_010588 was found to bind to BAG2, thereby inhibiting PINK1 ubiquitination and promoting its stabilization on damaged mitochondria. This activation of the PINK1/Parkin pathway increased mitophagy and pulmonary artery smooth muscle cell proliferation. SP1 was identified as a positive regulator of XLOC_010588 expression. Clinically, BAG2 levels were significantly elevated in patients with HPH. In vivo, BAG2 knockdown alleviated HPH in rats, confirming its role in disease progression. CONCLUSIONS:Our study reveals a novel mechanism in which XLOC_010588 promotes mitophagy via BAG2-dependent suppression of PINK1 ubiquitination, contributing to pulmonary artery smooth muscle cell proliferation and HPH development. These findings highlight the potential of targeting the XLOC_010588/BAG2/PINK1 axis for HPH treatment.

BACKGROUND:Administration of Paxlovid in early stage has been proved to reduce the risk of hospitalization or death by 89% in mild to moderate COVID-19 patients with high-risk. There were few evidences of Paxlovid in severe COVID-19 patients. RECOVERY study has previously shown that the use of glucocorticoids reduces the risk of death in hospitalized COVID-19 patients requiring oxygen or ventilatory support. The efficacy of Paxlovid plus glucocorticoids in COVID-19 patients with hypoxaemia is unclear. METHODS:In this multiple-centers prospective study, we collected the data of hospitalized adult Omicron infected subjects with hypoxaemia at 4 hospitals, who were treated with glucocorticoids or Paxlovid plus glucocorticoid. We compared the efficacy of Paxlovid plus glucocorticoids (P + GCS group) vs. glucocorticoids (GCS group). A 28-day composite outcome of disease progression was evaluated. RESULTS:Totally 266 Omicron infected patients with hypoxaemia were enrolled in this study. There was no difference in most of the baseline characteristics in two groups, including ages, sex and underlying diseases. The 28-day composite outcome in severe patients of P + GCS group was significantly lower than that of GCS group (16.9% vs. 33.8%, P = 0.013). The viral shedding time was shorter in P + GCS group than that in G group (6 days vs. 8 days, P = 0.015). The hospitalized time in severe patients of P + GCS group was significantly shorter than that of GCS group (15 days vs. 17 days, P = 0.0008). Cox analysis showed the benefit of P + GCS in sub-group of MODS, CRP ≥ 36 mg/L, d-dimer ≥1 µg/L, creatinine ≥ 90µmol/L). CONCLUSIONS:Our study demonstrated the benefit of Paxlovid plus glucocorticoid administration in hospitalized Omicron infection patients with hypoxaemia. These results, as least partly, supported direct evidence about the necessity of antiviral treatment in severe COVID-19 patients with hypoxaemia.

Pulmonary hypertension (PH) is a vascular disease characterized by remodeling of the pulmonary arteries and right heart failure. Chronic obstructive pulmonary disease (COPD) patients often have PH, which can worsen symptoms and raise morbidity and mortality. There are several reasons for increased pulmonary vascular resistance, pulmonary vascular remodeling, and ultimately the development of PH in COPD. These factors include genetics, inflammation caused by chemicals breathed, and changes in the alveoli seen in COPD and its physiology. Genes involved in mRNA conversion, subcellular localization, splicing, and translation are all finely tuned by RBPs in their post-transcriptional regulation. Erythropoietin regulates cytokines, chemokines, proteins, growth factors, and other pro-inflammatory mediators that change the lung microenvironment. Over the past few years, we have learned more about how RBPs act in PH and COPD. Here, we discuss the existing understanding of RBPs' location in the same pathogenic pathways shared by PH and COPD in order to emphasize their potential relevance as disease determinant/biomarker and, consequently, for possible therapeutic targeting.

BACKGROUND:Azvudine has become a widely used treatment for COVID-19 in China. Our study aimed to assess the real-world efficacy of azvudine in hospitalized COVID-19 patients during the omicron variant surge. METHODS:This multicenter retrospective cohort study was conducted at three hospitals, starting from December 2022. We developed a propensity-score matching (PSM) model to compare patients receiving azvudine with a control group. The primary outcome measured was a composite outcome, while secondary outcomes included all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. RESULTS:We enrolled a total of 7216 hospitalized COVID-19 patients, monitoring them for 28 days. Following PSM, we included 901 patients in both the azvudine group and the control group. The incidence of the composite outcome was 20.2 % in the azvudine group and 25.5 % in the control group (p = 0.007). The all-cause mortality rate was 10.0 % in the azvudine group and 13.7 % in the control group (p = 0.016). The intensive care unit admission was 15.5 % in the azvudine group and 19.6 % in the control group (p = 0.022). CONCLUSION:During the omicron epidemic in China, oral administration of azvudine was associated with a reduced risk of the composite outcome and all-cause mortality in COVID-19 patients.

Introduction:Associations of pulmonary function as evaluated by forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) with non-alcoholic fatty liver disease (NAFLD) have been reported in observational studies. Nevertheless, observational studies are susceptible to bias and reverse causality, making it difficult to infer the existence and direction of causality. We aimed to evaluate the causal effect of pulmonary function on NAFLD using the Mendelian randomization (MR) method. Material and methods:We performed univariate MR, multivariate MR, and bidirectional two-sample MR analyses to jointly assess the causal relationship between pulmonary function and NAFLD. In addition to the inverse variance weighting method as the primary MR analysis, three complementary methods were also performed. A series of sensitivity analyses were carried out to rule out pleiotropy. Results:We found that each genetically predicted (standard deviation) SD increase in FEV1 and FVC was associated with decreased NAFLD risk. However, after adjusting for height in the multivariate MR, only the effect of FEV1 on NAFLD risk remained significant. Furthermore, we found no causal effect of NAFLD on lung function in the reverse MR analysis. Conclusions:Our findings indicated that reduced lung function, especially FEV1, is causally associated with the risk of NAFLD. Although the mechanism remains unclear, FEV1 could be considered when assessing NAFLD risk and as a potential target for NAFLD prevention.

Background:Poly (ADP-Ribose) Polymerase (PARP) inhibitors represent a novel class of drugs that hinder DNA repair mechanisms in tumor cells, leading to cell death. This systematic review aims to evaluate the effectiveness, safety, and potential adverse effects of PARP inhibitors (PARPi) in the management of patients with advanced lung cancer.Materials and Methods:We conducted a comprehensive search for relevant studies in PubMed, Embase, Cochrane, and ClinicalTrials.gov. We extracted primary and secondary outcome measures, including progression-free survival (PFS), overall survival (OS), and adverse events (AEs), from the identified literature for subsequent meta-analysis and systematic review.Results:This study encompassed twelve randomized controlled trials, involving 3,132 patients with advanced lung cancer. In comparison to non-PARPi treatments, the administration of PARPi significantly extended OS (hazard ratio (HR) = 0.90, 95% CI = 0.83–0.97, p = 0.006). However, the difference in PFS did not reach statistical significance.Conclusion:In summary, therapies incorporating PARPi provide a degree of benefit by extending OS in patients with advanced lung cancer. Nonetheless, further trials are necessary to furnish additional evidence regarding the efficacy and safety of PARPi in the treatment of lung cancer.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier number: CRD42023424673.

BackgroundIn recent years, COVID-19 and tuberculosis have emerged as major infectious diseases, significantly contributing to global mortality as respiratory illnesses. There is increasing evidence of a reciprocal influence between these diseases, exacerbating their incidence, severity, and mortality rates.MethodsThis study involved retrieving COVID-19 and tuberculosis data from the GEO database and identifying common differentially expressed genes. Machine learning techniques, specifically random forest analysis, were applied to pinpoint key genes for diagnosing COVID-19. The Cibersort algorithm was employed to estimate immune cell infiltration in individuals with COVID-19. Additionally, single-cell sequencing was used to study the distribution of VNN1 within immune cells, and molecular docking provided insights into potential drugs targeting these critical prognosis genes.ResultsGMNN, SCD, and FUT7 were identified as robust diagnostic markers for COVID-19 across training and validation datasets. Importantly, VNN1 was associated with the progression of severe COVID-19, showing a strong correlation with clinical indicators and immune cell infiltration. Single-cell sequencing demonstrated a predominant distribution of VNN1 in neutrophils, and molecular docking highlighted potential pharmacological targets for VNN1.ConclusionsThis study enhances our understanding of the shared pathogenic mechanisms underlying tuberculosis and COVID-19, providing essential insights that could improve the diagnosis and treatment of severe COVID-19 cases.