Roles of LncRNAs in the Pathogenesis of Pulmonary Hypertension.

Pulmonary hypertension (PH) is a persistently progressive, incurable, multifactorial associated fatal pulmonary vascular disease characterized by pulmonary vascular remodeling. Long noncoding RNAs (lncRNAs) are involved in regulating pathological processes such as pulmonary vasoconstriction, thickening, remodeling, and inflammatory cell infiltration in PH by acting on different cell types. Because of their differential expression in PH patients, as demonstrated by the observation that some lncRNAs are significantly upregulated while others are significantly downregulated in PH patients, lncRNAs are potentially useful biomarkers for assessing disease progression and diagnosis or prognosis in PH patients. This article provides an overview of the different mechanisms by which lncRNAs are involved in the pathogenesis of PH.

Oxidative stress in acute pulmonary embolism: emerging roles and therapeutic implications.

Oxidative stress is an imbalance between the body's reactive oxygen species and antioxidant defense mechanisms. Oxidative stress is involved in the development of several cardiovascular diseases, such as pulmonary hypertension, atherosclerosis, and diabetes mellitus. A growing number of studies have suggested the potential role of oxidative stress in the pathogenesis of pulmonary embolism. Biomarkers of oxidative stress in pulmonary embolism have also been explored, such as matrix metalloproteinases, asymmetric dimethylarginine, and neutrophil/lymphocyte ratio. Here, we comprehensively summarize some oxidative stress mechanisms and biomarkers in the development of acute pulmonary embolism and summarize related treatments based on antioxidant stress to explore effective treatment strategies for acute pulmonary embolism.

Genetic association between smoking and DLCO in idiopathic pulmonary fibrosis patients.

BACKGROUND: Observational studies have shown that smoking is related to the diffusing capacity of the lungs for carbon monoxide (DLCO) in individuals with idiopathic pulmonary fibrosis (IPF). Nevertheless, further investigation is needed to determine the causal effect between these two variables. Therefore, we conducted a study to investigate the causal relationship between smoking and DLCO in IPF patients using two-sample Mendelian randomization (MR) analysis. METHODS: Large-scale genome-wide association study (GWAS) datasets from individuals of European descent were analysed. These datasets included published lifetime smoking index (LSI) data for 462,690 participants and DLCO data for 975 IPF patients. The inverse-variance weighting (IVW) method was the main method used in our analysis. Sensitivity analyses were performed by MR‒Egger regression, Cochran's Q test, the leave-one-out test and the MR-PRESSO global test. RESULTS: A genetically predicted increase in LSI was associated with a decrease in DLCO in IPF patients [ORIVW = 0.54; 95% CI 0.32-0.93; P = 0.02]. CONCLUSIONS: Our study suggested that smoking is associated with a decrease in DLCO. Patients diagnosed with IPF should adopt an active and healthy lifestyle, especially by quitting smoking, which may be effective at slowing the progression of IPF.

Detection of Severe Murine Typhus by Nanopore Targeted Sequencing, China.

We report a case of murine typhus in China caused by Rickettsia typhi and diagnosed by nanopore targeted sequencing of a bronchoalveolar lavage fluid sample. This case highlights that nanopore targeted sequencing can effectively detect clinically unexplained infections and be especially useful for detecting infections in patients without typical signs and symptoms.

Tracheal microbiome and metabolome profiling in iatrogenic subglottic tracheal stenosis.

BACKGROUND: To study the role of microecology and metabolism in iatrogenic tracheal injury and cicatricial stenosis, we investigated the tracheal microbiome and metabolome in patients with tracheal stenosis after endotracheal intubation. METHODS: We collected 16 protected specimen brush (PSB) and 8 broncho-alveolar lavage (BAL) samples from 8 iatrogenic subglottic tracheal stenosis patients, including 8 PSB samples from tracheal scar sites, 8 PSB samples from scar-free sites and 8 BAL samples, by lavaging the subsegmental bronchi of the right-middle lobe. Metagenomic sequencing was performed to characterize the microbiome profiling of 16 PSB and 8 BAL samples. Untargeted metabolomics was performed in 6 PSB samples (3 from tracheal scar PSB and 3 from tracheal scar-free PSB) using high-performance liquid chromatography‒mass spectrometry (LC‒MS). RESULTS: At the species level, the top four bacterial species were Neisseria subflava, Streptococcus oralis, Capnocytophaga gingivals, and Haemophilus aegyptius. The alpha and beta diversity among tracheal scar PSB, scar-free PSB and BAL samples were compared, and no significant differences were found. Untargeted metabolomics was performed in 6 PSB samples using LC‒MS, and only one statistically significant metabolite, carnitine, was identified. Pathway enrichment analysis of carnitine revealed significant enrichment in fatty acid oxidation. CONCLUSION: Our study found that carnitine levels in tracheal scar tissue were significantly lower than those in scar-free tissue, which might be a new target for the prevention and treatment of iatrogenic tracheal stenosis in the future.

Flu-IV score: a predictive tool for assessing the risk of invasive mechanical ventilation in patients with influenza-related pneumonia.

BACKGROUND: The need for invasive mechanical ventilation (IMV) is linked to significant morbidity and mortality in patients with influenza-related pneumonia (Flu-p). We aimed to develop an assessment tool to predict IMV among Flu-p patients within 14 days of admission. METHODS: In total, 1107 Flu-p patients from five teaching hospitals were retrospectively enrolled from January 2012 to December 2019, including 895 patients in the derivation cohort and 212 patients in the validation cohort. The predictive model was established based on independent risk factors for IMV in the Flu-p patients from the derivation cohort. RESULTS: Overall, 10.6% (117/1107) of patients underwent IMV within 14 days of admission. Multivariate regression analyses revealed that the following factors were associated with IMV: early neuraminidase inhibitor use (- 3 points), lymphocytes < 0.8 × 109/L (1 point), multi-lobar infiltrates (1 point), systemic corticosteroid use (1 point), age ≥ 65 years old (1 points), PaO2/FiO2 < 300 mmHg (2 points), respiratory rate ≥ 30 breaths/min (3 points), and arterial PH < 7.35 (4 points). A total score of five points was used to identify patients at risk of IMV. This model had a sensitivity of 85.5%, a specificity of 88.8%, and exhibited better predictive performance than the ROX index (AUROC = 0.909 vs. 0.594, p = 0.004), modified ROX index (AUROC = 0.909 vs. 0.633, p = 0.012), and HACOR scale (AUROC = 0.909 vs. 0.622, p < 0.001) using the validation cohort. CONCLUSIONS: Flu-IV score is a valuable prediction rule for 14-day IMV rates in Flu-p patients. However, it should be validated in a prospective study before implementation.

Regulation of circular RNAs act as ceRNA in a hypoxic pulmonary hypertension rat model.

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify. The significant DEcircRNAs/DEmiRNAs/DEmRNAs was showed, and a ceRNA network with 8 DEcircRNAs, 9 DEmiRNAs and 46 DEmRNAs were constructed. The functional enrichment suggested the inflammatory response, NF-κB signalling, MAPK cascade and Toll-like receptor were associated with HPH. Further assessment confirmed that circ_002723, circ_008021, circ_016925 and circ_020581 could have a potential ceRNA mechanism by sponging miR-23a or miR-21 to control downstream target gene and be involved in the pathophysiology of HPH. The qRT-PCR validation results were consistent with the RNA-Seq results. This study revealed potentially important genes, pathways and ceRNA regulatory networks in HPH.

Comparison of clinical characteristics and outcomes between respiratory syncytial virus and influenza-related pneumonia in China from 2013 to 2019.

This study aims to compare clinical characteristics and severity between adults with respiratory syncytial virus (RSV-p) and influenza-related pneumonia (Flu-p). A total of 127 patients with RSV-p, 693 patients with influenza A-related pneumonia (FluA-p), and 386 patients with influenza B-related pneumonia (FluB-p) were retrospectively reviewed from 2013 through 2019 in five teaching hospitals in China. A multivariate logistic regression model indicated that age ≥ 50 years, cerebrovascular disease, chronic kidney disease, solid malignant tumor, nasal congestion, myalgia, sputum production, respiratory rates ≥ 30 beats/min, lymphocytes < 0.8×109/L, and blood albumin < 35 g/L were predictors that differentiated RSV-p from Flu-p. After adjusting for confounders, a multivariate logistic regression analysis confirmed that, relative to RSV-p, FluA-p (OR 2.313, 95% CI 1.377-3.885, p = 0.002) incurred an increased risk for severe outcomes, including invasive ventilation, ICU admission, and 30-day mortality; FluB-p (OR 1.630, 95% CI 0.958-2.741, p = 0.071) was not associated with increased risk. Some clinical variables were useful for discriminating RSV-p from Flu-p. The severity of RSV-p was less than that of FluA-p, but was comparable to FluB-p.

The severity and risk factors for mortality in immunocompromised adult patients hospitalized with influenza-related pneumonia.

OBJECTIVE: To explore disease severity and risk factors for 30-day mortality of adult immunocompromised (IC) patients hospitalized with influenza-related pneumonia (Flu-p). METHOD: A total of 122 IC and 1191 immunocompetent patients hospitalized with Flu-p from January 2012 to December 2018 were recruited retrospectively from five teaching hospitals in China. RESULTS: After controlling for confounders, multivariate logistic regression analysis showed that immunosuppression was associated with increased risks for invasive ventilation [odds ratio: (OR) 2.475, 95% confidence interval (CI): 1.511-4.053, p < 0.001], admittance to the intensive care unit (OR: 3.247, 95% CI 2.064-5.106, p < 0.001), and 30-day mortality (OR: 3.206, 95% CI 1.926-5.335, p < 0.001) in patients with Flu-p. Another multivariate logistic regression model revealed that baseline lymphocyte counts (OR: 0.993, 95% CI 0.990-0.996, p < 0.001), coinfection (OR: 5.450, 95% CI 1.638-18.167, p = 0.006), early neuraminidase inhibitor therapy (OR 0.401, 95% CI 0.127-0.878, p = 0.001), and systemic corticosteroid use at admission (OR: 6.414, 95% CI 1.348-30.512, p = 0.020) were independently related to 30-day mortality in IC patients with Flu-p. Based on analysis of the receiver operating characteristic curve (ROC), the optimal cutoff for lymphocyte counts was 0.6 × 109/L [area under the ROC (AUROC) = 0.824, 95% CI 0.744-0.887], sensitivity: 97.8%, specificity: 73.7%]. CONCLUSIONS: IC conditions are associated with more severe outcomes in patients with Flu-p. The predictors for mortality that we identified may be valuable for the management of Flu-p among IC patients.

FluA-p score: a novel prediction rule for mortality in influenza A-related pneumonia patients.

BACKGROUND: The pneumonia severity index (PSI) and the CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) score have been shown to predict mortality in community-acquired pneumonia. Their ability to predict influenza-related pneumonia, however, is less well-established. METHODS: A total of 693 laboratory-confirmed FluA-p patients diagnosed between Jan 2013 and Dec 2018 and recruited from five teaching hospitals in China were included in the study. The sample included 494 patients in the derivation cohort and 199 patients in the validation cohort. The prediction rule was established based on independent risk factors for 30-day mortality in FluA-p patients from the derivation cohort. RESULTS: The 30-day mortality of FluA-p patients was 19.6% (136/693). The FluA-p score was based on a multivariate logistic regression model designed to predict mortality. Results indicated the following significant predictors (regression statistics and point contributions toward total score in parentheses): blood urea nitrogen > 7 mmol/L (OR 1.604, 95% CI 1.150-4.492, p = 0.040; 1 points), pO2/FiO2 ≤ 250 mmHg (OR 2.649, 95% CI 1.103-5.142, p = 0.022; 2 points), cardiovascular disease (OR 3.967, 95% CI 1.269-7.322, p < 0.001; 3 points), arterial PH < 7.35 (OR 3.959, 95% CI 1.393-7.332, p < 0.001; 3 points), smoking history (OR 5.176, 95% CI 2.604-11.838, p = 0.001; 4 points), lymphocytes < 0.8 × 109/L (OR 8.391, 95% CI 3.271-16.212, p < 0.001; 5 points), and early neurominidase inhibitor therapy (OR 0.567, 95% CI 0.202-0.833, p = 0.005; - 2 points). Seven points was used as the cut-off value for mortality risk stratification. The model showed a sensitivity of 0.941, a specificity of 0.762, and overall better predictive performance than the PSI risk class (AUROC = 0.908 vs 0.560, p < 0.001) and the CURB-65 score (AUROC = 0.908 vs 0.777, p < 0.001). CONCLUSIONS: Our results showed that a FluA-p score was easy to derive and that it served as a reliable prediction rule for 30-day mortality in FluA-p patients. The score could also effectively stratify FluA-p patients into relevant risk categories and thereby help treatment providers to make more rational clinical decisions.

Impact of early neuraminidase inhibitor treatment on clinical outcomes in patients with influenza B-related pneumonia: a multicenter cohort study.

The aim of this study is to evaluate the impact of early (within 2 days after disease onset) neuraminidase inhibitor (NAI) administration on clinical outcomes in patients with laboratory-confirmed influenza B-related pneumonia (FluB-p). This was a multicenter study conducted from 1 January 2013 to 1 May 2019. Data of immunocompetent adult and adolescent FluB-p patients hospitalized at five different teaching hospitals in China were retrospectively collected, including demographic and clinical features as well as clinical and treatment outcomes. Univariate and multivariate logistic regression analyses were performed to assess the effects of early NAI administration on clinical outcomes in FluB-p patients. In total, 386 hospitalized patients with community-onset FluB-p were included in this study, of whom 39.6% (153/386) were treated with NAI early. After adjusting for the weighted propensity scores of treatment, systemic corticosteroid, and antibiotic uses, the results of multivariate logistic regression model indicated that early NAI treatment was associated with the decreased risks of invasive ventilation [odd ratio (OR) 0.325, 95% confidence interval (CI) 0.123-0.858; p = 0.023), admittance to intensive care unit (OR 0.425, 95% CI 0.204-0.882; p = 0.022), and 30-day mortality (OR 0.416, 95% CI 0.184-0.944, p = 0.036)] in FluB-p patients. In addition, the multivariate logistic regression analysis revealed that early NAI treatment (OR 0.306, 95% CI 0.063-0.618; p = 0.010) was an independent predictor for 30-day mortality in patients with FluB-p. Early NAI treatment was associated with better clinical outcomes in FluB-p patients, which supports the recommendations of its use in severe influenza illness.

The impact of early neuraminidase inhibitor therapy on clinical outcomes in patients hospitalised with influenza A-related pneumonia: a multicenter, retrospective study.

BACKGROUND: Guidelines emphasize prompt antiviral treatment in severe influenza patients. Although nearly a 50% of severe influenza present with pneumonia, the effect of early (≤ 2 days after illness onset) neuraminidase inhibitor (NAI) use on the clinical outcomes of influenza A-related pneumonia (FluA-p) has rarely been assessed. Furthermore, data about the administration of NAIs in the real-world management of Flu-p in China are limited. METHODS: Data of patients hospitalised with FluA-p from five teaching hospitals in China from 1 January 2013 to 31 December 2018 were reviewed retrospectively. The impact of early NAI therapy on the outcomes in FluA-p patients, and the indications of early NAI administration by clinicians were evaluated by logistic regression analysis. RESULTS: In total, 693 FluA-p patients were included. Of these patients, 33.5% (232/693) were treated early. After adjusting for weighted propensity scores for treatment, systemic corticosteroid and antibiotic use, a multivariate logistic regression model showed that early NAI therapy was associated with decreased risk for invasive ventilation [odds ratio (OR) 0.511, 95% confidence interval (CI) 0.312-0.835, p = 0.007) and 30-day mortality (OR 0.533, 95% CI 0.210-0.807, p < 0.001) in FluA-p patients. A multivariate logistic regression model confirmed early NAI use (OR 0.415, 95% CI 0.195-0.858, p = 0.001) was a predictor for 30-day mortality in FluA-p patients and a positive rapid influenza diagnostic test was the only indication (OR 3.586, 95% CI 1.259-10.219, p < 0.001) related to the prescription of early NAI by clinicians. CONCLUSIONS: Early NAI therapy is associated with better outcomes in FluA-p patients. Improved education and training of clinicians on the guidelines of influenza are needed.

Disease burden and prognostic factors for clinical failure in elderly community acquired pneumonia patients.

BACKGROUND: The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP). METHODS: 3011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis. RESULTS: The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH < 7.3, PaO2/FiO2 < 200 mmHg, sodium < 130 mmol/L, healthcare-associated pneumonia, white blood cells > 10,000/mm3, pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors. CONCLUSIONS: Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP. TRIAL REGISTRATION: A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb.

Invasive pulmonary aspergillosis in immunocompetent patients hospitalised with influenza A-related pneumonia: a multicenter retrospective study.

BACKGROUND: Increasing cases of pulmonary aspergillosis (IPA) in immunocompetent patients with severe influenza have been reported. Howevere, the risk factors for occurence and death are largely unknown. METHODS: Data of hospitalised patients with influenza A-related pneumonia (FluA-p) obtained from five teaching hospitals from 2031 to 2018, were reviewed. Univariate and multivariate logistical regression analyses were performed to determine the risk factors involved in the acquisition and 60-day mortality in IPA patients. RESULTS: Of the 693 FluA-p patients included in the study, 3.0% (21/693) were IPA patients with a 60-day mortality of 42.9% (9/21). Adjusted for confounders, a Cox proportional hazard model showed that IPA was associated with increased risk for 60-day mortality [hazard ratio (HR) 4.336, 95% confidence interval (CI) 1.191-15.784, p = 0.026] in FluA-p patients. A multivariate logistic regression model confirmed that age (odd ratio (OR) 1.147, 95% CI 1.048-1.225, p = 0.003), systemic corticosteroids use before IPA diagnosis (OR 33.773, 95% CI 5.681-76.764, p <  0.001), leukocytes > 10 × 109/L (OR 1.988, 95% CI 1.028-6.454, p = 0.029) and lymphocytes < 0.8 × 109/L on admission (OR 34.813, 95% CI 1.676-73.006, p = 0.022), were related with the acquisition of IPA. Early neuraminidase inhibitor use (OR 0.290, 95% CI 0.002-0.584, p = 0.021) was associated with a decreased risk for a 60-day mortality in IPA patients. CONCLUSIONS: Our results showed that IPA worsen the clinical outcomes of FluA-p patients. The risk factors for the acquisition and death were helpful for the clinicians in preventing and treating IPA.

Autophagy in pulmonary hypertension: Emerging roles and therapeutic implications.

Autophagy is an important mechanism for cellular self-digestion and basal homeostasis. This gene- and modulator-regulated pathway is conserved in cells. Recently, several studies have shown that autophagic dysfunction is associated with pulmonary hypertension (PH). However, the relationship between autophagy and PH remains controversial. In this review, we mainly introduce the effects of autophagy-related genes and some regulatory molecules on PH and the relationship between autophagy and PH under the conditions of hypoxia, monocrotaline injection, thromboembolic stress, oxidative stress, and other drugs and toxins. The effects of other autophagy-related drugs, such as chloroquine, 3-methyladenine, rapamycin, and other potential therapeutic drugs and targets, in PH are also described.

MicroRNA-214-3p Regulates Hypoxia-Mediated Pulmonary Artery Smooth Muscle Cell Proliferation and Migration by Targeting ARHGEF12.

BACKGROUND miR-214-3p has been found to inhibit proliferation and migration in cancer cells. The objective of this study was to determine whether ARHGEF12 is involved in miR-214-3p-mediated suppression of proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). MATERIAL AND METHODS PASMCs were cultured under normoxia or hypoxia. miR-214-3p mimics or inhibitors were transiently transfected into PASMCs. Proliferation, apoptosis, and migration of PASMCs were evaluated using MTT assay, flow cytometry, and Boyden chamber apparatus. Western blot analysis was used to examine expression of Rho guanine nucleotide exchange factor 12 (ARHGEF12), c-fos, c-jun, and caspase-3. Luciferase reporter assay was used to test the direct regulation of miR-214-3p on the 3'-untranslated region (UTR) of ARHGEF12. RESULTS miR-214-3p was significantly upregulated in hypoxia-treated PASMCs. Knockdown of miR-214-3p significantly attenuated hypoxia-induced proliferation and migration in PASMCs and promoted apoptosis, whereas this effect was aggravated by overexpression of miR-214-3p. In addition, dual-luciferase reporter assay demonstrated that ARHGEF12 is a direct target gene of miR-214-3p. The protein levels of ARHGEF12 were downregulated after knockdown of miR-214-3p in PASMCs. Rescue experiment results indicated that decreased proliferation of PASMCs resulted from knockdown of miR-214-3p were partially reversed by silencing of ARHGEF12 by siRNA. Furthermore, knockdown of miR-214-3p reduced expression of c-jun and c-fos, but increased expression of caspase-3 in PASMCs under hypoxia. CONCLUSIONS In conclusion, these results indicate that miR-214-3p acts as a novel regulator of hypoxia-induced proliferation and migration by directly targeting ARHGEF12 and dysregulating c-jun and c-fos in PASMCs, and may be a potential therapeutic target for treating pulmonary hypertension.

Effects of age, comorbidity and adherence to current antimicrobial guidelines on mortality in hospitalized elderly patients with community-acquired pneumonia.

BACKGROUND: Limited information exists on the clinical characteristics predictive of mortality in patients aged ≥65 years in many countries. The impact of adherence to current antimicrobial guidelines on the mortality of hospitalized elderly patients with community-acquired pneumonia (CAP) has never been assessed. METHODS: A total of 3131 patients aged ≥65 years were enrolled from a multi-center, retrospective, observational study initiated by the CAP-China network. Risk factors for death were screened with multivariable logistic regression analysis, with emphasis on the evaluation of age, comorbidities and antimicrobial treatment regimen with regard to the current Chinese CAP guidelines. RESULTS: The mean age of the study population was 77.4 ± 7.4 years. Overall in-hospital and 60-day mortality were 5.7% and 7.6%, respectively; these rates were three-fold higher in those aged ≥85 years than in the 65-74 group (11.9% versus 3.2% for in-hospital mortality and 14.1% versus 4.7% for 60-day mortality, respectively). The mortality was significantly higher among patients with comorbidities compared with those who were otherwise healthy. According to the 2016 Chinese CAP guidelines, 62.1% of patients (1907/3073) received non-adherent treatment. For general-ward patients without risk factors for Pseudomonas aeruginosa (PA) infection (n = 2258), 52.3% (1094/2090) were over-treated, characterized by monotherapy with an anti-pseudomonal ß-lactam or combination with fluoroquinolone + ß-lactam; while 71.4% of intensive care unit (ICU) patients (120/168) were undertreated, without coverage of atypical bacteria. Among patients with risk factors for PA infection (n = 815), 22.9% (165/722) of those in the general ward and 74.2% of those in the ICU (69/93) were undertreated, using regimens without anti-pseudomonal activity. The independent predictors of 60-day mortality were age, long-term bedridden status, congestive heart failure, CURB-65, glucose, heart rate, arterial oxygen saturation (SaO2) and albumin levels. CONCLUSIONS: Overtreatment in general-ward patients and undertreatment in ICU patients were critical problems. Compliance with Chinese guidelines will require fundamental changes in standard-of-care treatment patterns. The data included herein may facilitate early identification of patients at increased risk of mortality. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov ( NCT02489578 ).

Lymphatic vessel density as a prognostic indicator in Asian NSCLC patients: a meta-analysis.

BACKGROUND: To determine the association of lymphatic vessel density (LVD) with the prognosis of Asian non-small cell lung cancer (NSCLC) patients via a meta-analysis. METHODS: Eligible studies were selected by searching PubMed and EMBASE from inception to July 25, 2017. The reference lists of the retrieved articles were also consulted. The information was independently screened by two authors. When heterogeneity was significant, a random-effects model was used to determine overall pooled risk estimates. RESULTS: A total of 15 studies with 1075 patients were finally included in the meta-analysis. LVD was positively associated with the prognosis of NSCLC in the overall analysis (hazard ratio (HR) 1.14, 95% confidence interval (95% CI): 1.02-1.27, p = 0.000, I2 = 73.2%). Subgroup analyses were performed on 5 VEGFR-3 groups (p = 0.709, I2 = 0.0%), 3 LYVE-1 groups (p = 0.01, I2 = 86.4%), 5 D2-40 groups (p = 0.019, I2 = 66.2%), and 2 podoplanin groups (p = 0.094, I2 = 64.5%). Sensitivity analysis indicated robust results. There was no publication bias. CONCLUSIONS: LVD is an indicator of poor prognosis in Asian NSCLC patients.

Successful endoscopic closure of alveolar-pleural fistula due to Aspergillus empyema using a ventricular septal defect occluder.

We report a patient with fever and cough for 2 months who was finally given a diagnosis of alveolar-pleural fistula due to aspergillus empyema. We successfully closed the alveolar-pleural fistula with a ventricular septal defect occluder through bronchoscopy. Endoscopic closure of an alveolar-pleural fistula with ventricular septal defect occluder is worth being explored.

Disordered gut microbiota and alterations in the serum metabolome are associated with venous thromboembolism.

INTRODUCTION: The gut microbiome plays a crucial role in various diseases, and its regulation is a potential treatment option for these conditions. However, the relationship between the gut microbiome and venous thromboembolism (VTE) remains poorly explored. METHODS: In this study, we collected feces and serum samples from 8 VTE patients and 7 healthy controls. The gut microbiota and serum metabolites were analyzed using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Additionally, a combined analysis of microbiota and metabolome was performed. RESULTS: The alpha and beta diversity between the VTE and control groups were significantly different. Patients with VTE exhibited an overgrowth of Blautia, Roseburia, Coprococcus, and Ruminococcus. Moreover, serum metabolomics analysis revealed altered levels of choline and lithocholic acid. Pathway enrichment analysis indicated a significant upregulation of bile secretion pathways. In addition, a positive correlation was observed between the levels of serum choline and lithocholic acid and the abundance of gut flora enriched in the VTE group. CONCLUSION: This study provided novel insights into the disordered gut microbiota and serum metabolome associated with VTE, suggesting potential common pathological mechanisms between VTE and arterial thrombosis. Targeted modulation of the gut microbiome may hold promise as a preventive and therapeutic approach for VTE.