Identifying an immunogenic cell death-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma.

BACKGROUND: Immunogenic cell death (ICD) is a regulated form of cell death that triggers an adaptive immune response. The objective of this study was to investigate the correlation between ICD-related genes (ICDGs) and the prognosis and the immune microenvironment of patients with lung adenocarcinoma (LUAD). METHODS: ICD-associated molecular subtypes were identified through consensus clustering. Subsequently, a prognostic risk model comprising 5 ICDGs was constructed using Lasso-Cox regression in the TCGA training cohort and further tested in the GEO cohort. Enriched pathways among the subtypes were analyzed using GO, KEGG, and GSVA. Furthermore, the immune microenvironment was assessed using ESTIMATE, CIBERSORT, and ssGSEA analyses. RESULTS: Consensus clustering divided LUAD patients into three ICDG subtypes with significant differences in prognosis and the immune microenvironment. A prognostic risk model was constructed based on 5 ICDGs and it was used to classify the patients into two risk groups; the high-risk group had poorer prognosis and an immunosuppressive microenvironment characterized by low immune score, low immune status, high abundance of immunosuppressive cells, and high expression of tumor purity. Cox regression, ROC curve analysis, and a nomogram indicated that the risk model was an independent prognostic factor. The five hub genes were verified by TCGA database, cell sublocalization immunofluorescence analysis, IHC images and qRT-PCR, which were consistent with bioinformatics analysis. CONCLUSIONS: The molecular subtypes and a risk model based on ICDGs proposed in our study are both promising prognostic classifications in LUAD, which may provide novel insights for developing accurate targeted cancer therapies.

Serum Albumin for Short-Term Poor Prognosis in Patients With Acute Pulmonary Embolism: A Clinical Study Based on a Database.

The relationship between serum albumin (ALB) and short-term prognosis in patients with acute pulmonary embolism (APE) remains unclear. We investigated the predictive value of ALB for short-term prognosis in APE patients using our hospital pulmonary embolism (PE) database (384 patients consecutively collected). Logistic regression analysis and nomograms were applied to construct the predictive model, and validation was assessed. A total of 340 APE patients were included, with a 30-day all-cause mortality rate of 8.5%. The incidence of hypoalbuminemia was 15.9%. The odds ratio (OR) for short-term mortality in patients with high ALB was 0.89 (0.886, 95% CI: 0.812-0.967). Additionally, we created a nomogram for individualized mortality risk prediction. Receiver operating characteristic (ROC) curve analysis showed that the diagnostic area under the curve (AUC) of ALB was 0.758 (95% CI 0.683-0.833), and the best cut-off value was 33.85 g/L. Optimal simplified Pulmonary Embolism Severity Index (sPESI) (ALB combined sPESI) AUC was 0.835 (95% CI 0.775-0.896). Baseline hypoalbuminemia may be an independent prognostic indicator of short-term mortality in patients with APE.

Bioinformatics and Machine Learning Methods Identified MGST1 and QPCT as Novel Biomarkers for Severe Acute Pancreatitis.

Severe acute pancreatitis (SAP) is a life-threatening gastrointestinal emergency. The study aimed to identify biomarkers and investigate molecular mechanisms of SAP. The GSE194331 dataset from GEO database was analyzed using bioinformatics. Differentially expressed genes (DEGs) associated with SAP were identified, and a protein-protein interaction network (PPI) was constructed. Machine learning algorithms were used to determine potential biomarkers. Gene set enrichment analysis (GSEA) explored molecular mechanisms. Immune cell infiltration were analyzed, and correlation between biomarker expression and immune cell infiltration was calculated. A competing endogenous RNA network (ceRNA) was constructed, and biomarker expression levels were quantified in clinical samples using RT-PCR. 1101 DEGs were found, with two modules most relevant to SAP. Potential biomarkers in peripheral blood samples were identified as glutathione S-transferase 1 (MGST1) and glutamyl peptidyltransferase (QPCT). GSEA revealed their association with immunoglobulin regulation, with QPCT potentially linked to pancreatic cancer development. Correlation between biomarkers and immune cell infiltration was demonstrated. A ceRNA network consisting of 39 nodes and 41 edges was constructed. Elevated expression levels of MGST1 and QPCT were verified in clinical samples. In conclusion, peripheral blood MGST1 and QPCT show promise as SAP biomarkers for diagnosis, providing targets for therapeutic intervention and contributing to SAP understanding.

Stroke risk of COPD patients and death risk of COPD patients following a stroke: A systematic review and meta-analysis.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is closely related to the development and progression of cardiovascular disease. The purpose of this study is to clarify the answers to the following questions through systematic evaluation: the risk of stroke in COPD patients; the risk of stroke in acute exacerbations of COPD (AECOPD) patients; and the risk of death after stroke in COPD patients. METHODS: Two reviewers independently searched EMbase, PubMed, and the Cochrane Library for relevant literature from the date of creation to February 17, 2023, for studies relating COPD to stroke patients. Of the 8039 publications retrieved, we identified 27 articles that met our selection criteria. Fixed-effects or random-effects models were used to calculate ORs and 95% confidence intervals for the combined risk. RESULTS: combining studies on stroke risk in COPD patients by random-effects model suggested that COPD was an independent risk factor for stroke-associated pneumonia (OR 1.40, 95% CI: 1.24-1.59, I2 = 98.4%, P = .000), with significant heterogeneity in the results, and subgroup analysis did not find a source of heterogeneity. In the combined 7 AECOPD studies, a significantly higher risk of stroke was found (OR 1.53, 95% CI: 1.44-1.63, I2 = 49.2%, P = .066). In the combined 6 short- term prognostic studies, the relationship between COPD and risk of death was not highly significant (OR 1.12, 95% CI: 1.08-1.16, I2 = 37.4%, P = .131). In 10 long-term observational prognosis studies, COPD was suggested to be associated with death after stroke by combining data using a random-effects model (OR 1.20, 95% CI: 1.13-1.27, I2 = 56.8%, P = .014), and there was moderate heterogeneity in the combination, with subgroup analysis showing that stroke type may be a source of heterogeneity and the risk of death from ischemic stroke: OR 1.23, 95% CI: 1.17-1.29, I2 = 45.0%, P = .191 and the risk of death from both types of stroke: OR 1.12, 95% CI: 1.07-1.18, I2 =18.9%, P = .291. CONCLUSION: COPD is an independent risk factor for stroke. The risk of stroke is significantly increased, especially during AECOPD. In addition, the association between COPD and short-term death in stroke patients is insignificant, while it is more associated with fatal events in the long-term prognosis.

Association between diabetes and venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus (DM) plays a vital role in the development of cardiovascular disease. However, its association with venous thromboembolism (VTE) remains unclear, for the published study results are conflicting. We performed a meta-analysis of published cohort studies and case-control studies to assess the role of DM in the formation and prognosis of VTE. METHODS: PubMed and EMBASE databases were searched for articles from the database's establishment until September 15, 2022. Of the 15,754 publications retrieved, 50 studies were identified that met the selection criteria. The New castle-Ottawa Scale was used to evaluate the quality of the literature. Pooled odds ratios (ORs) and 95% confidence intervals were calculated using fixed- or random-effect models. RESULTS: We combined OR using a random-effects or fixed-effects model: patients with DM had an increased risk of VTE (OR 1.27, 95% confidence interval [CI]: 1.15-1.41), which still showed a partial association in studies adjusted by confounding factors (OR 1.20, 95% CI: 1.07-1.35). DM was not significantly associated with VTE when analyzed in studies adjusted by body mass index (OR 1.04, 95% CI: 0.94-1.15). VTE patients with DM had a higher risk of short-term and long-term mortality than those without DM (OR 1.58 [95% CI: 1.26-1.99] for long-term mortality and OR 1.20 [95% CI: 1.19-1.21] for short-term mortality). CONCLUSION: There was no significant association between DM and VTE risk, and body mass index may be a significant confounding factor between DM and VTE risk. However, DM can still lead to an increased risk of long-term and short-term mortality in patients with VTE.

Efficacy and safety of macitentan for pulmonary hypertension: A meta-analysis.

INTRODUCTION: Our purpose of this study is to evaluate the effect and safety of macitentan in the treatment of pulmonary hypertension (PH). METHODS: We retrieved the safety and efficacy of macitentan treatment for PH using PubMed, the Cochrane Library, EMBASE databases and clinicaltrials.gov. The Cochrane Risk of Bias Tool was used for literature screening and quality assessment. Data analysis was conducted using RevMan 5.4.1 and Stata/SE 15.1 software. Results are presented as standardization mean differences (SMDs) and odds ratio (OR). RESULTS: Meta-analysis of seven randomized controlled trial (RCT) studies and four non-RCT studies with 2769 patients was included, involving 723 in the macitentan group and 599 in the placebo group. The results of the study showed that macitentan had effectively decreased pulmonary vascular resistance (PVR) (SMD = -0.53, 95% CI: -0.77--0.29, p < 0.05), cardiac index (CI) (SMD = 0.60, 95% CI: 0.37-0.83, p < 0.05) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (SMD = -0.22, 95% CI: -0.40--0.03, p < 0.05). Furthermore, macitentan also significantly reduced PVR (SMD = -0.58, 95% CI: -0.80--0.35, p < 0.05), 6-min walk distance (6WMD) (SMD = 0.33, 95% CI: 0.15-0.50, p < 0.05), CI (SMD = 0.48, 95% CI: 0.28-0.69, p < 0.05), mean pulmonary arterial pressure (mPAP) (SMD = -0.43, 95% CI: -0.64--0.23, p < 0.05) and NT-proBNP (SMD = -0.55, 95% CI: -1.07--0.03, p < 0.05) between baseline and follow-up. The adverse reactions to macitentan were mild, with headache, anaemia and bronchitis. Other efficacy and safety outcomes did not reach statistical differences. CONCLUSION: Macitentan therapy for PH is effective and safe. The effectiveness on PVR, mPAP, mean right atrial pressure (mRAP), mortality and other indicators still needs to be further confirmed.

Identification of cough-variant asthma phenotypes based on clinical and pathophysiologic data.

BACKGROUND: Cough-variant asthma (CVA) may respond differently to antiasthmatic treatment. There are limited data on the heterogeneity of CVA. OBJECTIVE: We aimed to classify patients with CVA using cluster analysis based on clinicophysiologic parameters and to unveil the underlying molecular pathways of these phenotypes with transcriptomic data of sputum cells. METHODS: We applied k-mean clustering to 342 newly physician-diagnosed patients with CVA from a prospective multicenter observational cohort using 10 prespecified baseline clinical and pathophysiologic variables. The clusters were compared according to clinical features, treatment response, and sputum transcriptomic data. RESULTS: Three stable CVA clusters were identified. Cluster 1 (n = 176) was characterized by female predominance, late onset, normal lung function, and a low proportion of complete resolution of cough (60.8%) after antiasthmatic treatment. Patients in cluster 2 (n = 105) presented with young, nocturnal cough, atopy, high type 2 inflammation, and a high proportion of complete resolution of cough (73.3%) with a highly upregulated coexpression gene network that related to type 2 immunity. Patients in cluster 3 (n = 61) had high body mass index, long disease duration, family history of asthma, low lung function, and low proportion of complete resolution of cough (54.1%). TH17 immunity and type 2 immunity coexpression gene networks were both upregulated in clusters 1 and 3. CONCLUSION: Three clusters of CVA were identified with different clinical, pathophysiologic, and transcriptomic features and responses to antiasthmatics treatment, which may improve our understanding of pathogenesis and help clinicians develop individualized cough treatment in asthma.

Prevalence, Risk Factor and Clinical Characteristics of Venous Thrombus Embolism in Patients with Acute Exacerbation of COPD: A Prospective Multicenter Study.

Background and Objective: The prevalence of venous thrombus embolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) is higher than in patients without COPD. Owing to the similarity of clinical symptoms between PE and acute exacerbation COPD (AECOPD), PE is likely to be overlooked or underdiagnosed in patients with AECOPD. The aim of the study was to investigate the prevalence, risk factor, clinical characteristics, and prognostic impact of VTE in patients with AECOPD. Methods: This multicenter, prospective, cohort study was conducted in 11 research centers of China. Data on the baseline characteristics, VTE-related risk factors, clinical symptoms, laboratory examination results, computed tomography pulmonary angiography (CTPA) and lower limb venous ultrasound of AECOPD patients were collected. Patients were followed up for 1 year. Results: A total of 1580 AECOPD patients were included in the study. The mean (SD) age was 70.4 (9.9) years and 195 (26%) patients were women. The prevalence of VTE was 24.5% (387/1580) and PE was 16.8% (266/1580). VTE patients were older; had higher BMI; and longer course of COPD than non-VTE patients. The history of VTE, cor pulmonale, less purulent sputum, increased respiratory rate, higher D-dimer, and higher NT-proBNP/BNP were independently associated with VTE in hospitalized patients with AECOPD. The mortality at 1-year was higher in patients with VTE than patients without VTE (12.9% vs 4.5%, p<0.01). There was no significant difference in the prognosis of patients with PE in segmental or subsegmental arteries and in main pulmonary arteries or lobar arteries (P>0.05). Conclusion: VTE is common in COPD patients and is associated with poor prognosis. Patients with PE at different locations had poorer prognosis than patients without PE. It is necessary to perform active screening strategy for VTE in AECOPD patients with risk factors.

Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population.

BACKGROUND: A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. METHODS: We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. RESULTS: After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10-14), ABO rs582094 (p-value = 1.16 × 10-10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10-17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. CONCLUSIONS: We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development.

Effectiveness of Lianhua Qingwen Capsule in Treatment of Asymptomatic COVID-19 Patients: A Randomized, Controlled Multicenter Trial.

Background: Asymptomatic patients are unneglected sources in propagating transmission chain due to their high viral loads. However, treatments available based on symptoms seem not applicable to asymptomatic patients. In this study, the authors want to estimate the effectiveness of Lianhua Qingwen (LH) capsule on asymptomatic coronavirus disease 2019 (COVID-19) patients. Methods: A randomized controlled trial (RCT) was performed to explore the effectiveness and safety of LH capsule in treating asymptomatic COVID-19 patients. Patients were randomized to control group (isolated observation) and treatment group (LH, 4 capsules, thrice daily) for 14 days. The primary endpoints were the rate and time of nucleic acid turning negative during the isolation observation. Results: A total of 120 participants were included in the full analysis set (60 each in the control and treatment groups). Data showed that the rate of nucleic acid turning negative during the isolation observation in the treatment group was higher than that in the control group (rate difference: 21.66%, 95% confidence interval [CI]: 4.34 to 37.27, p = 0.0142). Patients in the treatment group have a shorter time of nucleic acid turning negative (7.5 vs. 14.5 days, p = 0.018). Moreover, the rate of clinical symptoms appearance in the treatment group was lower compared with that in the control group (rate difference: -31.67, 95% CI: -46.83 to -13.82, p = 0.0005). The proportion of confirmed mild and common cases in the treatment group was also lower (35.00% vs. 66.67%, p = 0.0005). No serious adverse events were documented. Conclusions: In this study, the authors illustrated that LH capsule is beneficial to asymptomatic COVID-19 patients. Considering the lack of interventions for treating asymptomatic COVID-19 patients at this stage, LH capsule could be considered as a choice. Chinese Clinical Trial Registry: ChiCTR2100042066.

Characteristics of different asthma phenotypes associated with cough: a prospective, multicenter survey in China.

BACKGROUND: Asthma is a heterogeneous disease with variable symptoms, which presents with cough either as the sole or predominant symptom with or without wheezing. We compared the clinical and pathophysiological characteristics of cough predominant asthma (CPA), cough variant asthma (CVA) and classic asthma (CA) in order to determine any differential phenotypic traits. METHODS: In 20 clinics across China, a total of 2088 patients were finally recruited, including 327 CVA, 1041 CPA and 720 CA patients. We recorded cough and wheezing visual analogue scale, Leicester cough questionnaire (LCQ) and asthma control test scores. Fractional exhaled nitric oxide (FeNO), induced sputum cell counts, and capsaicin cough challenge were also measured and compared. RESULTS: CPA patients more frequently presented with cough as the initial symptom, and laryngeal symptoms (p < 0.001), had less symptoms related with rhinitis/sinusitis and gastroesophageal reflux (p < 0.05) than CA patients. Comorbidities including rhinitis and gastroesophageal reflux were similar, while the proportion of COPD and bronchiectasis was higher in CA patients. There were no differences in FeNO levels, sputum eosinophil and neutrophil counts, FEV1 (%pred) decreased from CVA to CPA to CA patients (p < 0.001). Cough sensitivity was higher in CVA and CPA compared to CA (p < 0.001), and was positively correlated with LCQ scores. CONCLUSIONS: CVA, CPA and CA can be distinguished by the presence of laryngeal symptoms, cough sensitivity and airflow obstruction. Asthma-associated chronic cough was not associated with airway inflammation or comorbidities in our cohort. Trial registration The Chinese Clinical Trial Registration Center, ChiCTR-POC-17011646, 13 June 2017.

Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

A Nomogram for Predicting the Risk of Pulmonary Hypertension for Patients with Chronic Obstructive Pulmonary Disease.

Background: Pulmonary hypertension (PH) is a life-threatening complication of chronic obstructive pulmonary disease (COPD). Timely diagnosis of PH in COPD patients is vital to achieve proper treatment; however, there is no algorithm to identify those at high risk. We aimed to develop a predictive model for PH in patients with COPD that provides individualized risk estimates. Methods: A total of 527 patients with COPD who were admitted to our hospital between May 2019 and December 2020 were retrospectively enrolled in this study. Using echocardiographic results as a standard, patients were stratified into a moderate- or high-PH probability group and a low-PH probability group. They were randomly grouped into either the training set (n = 368 patients) or validation set (n = 159 patients) in a ratio of 7:3. We utilized the least absolute shrinkage and selection operator (LASSO) regression model to select the feature variables. The characteristic variables selected in the LASSO regression were analyzed using multivariable logistic regression to construct the predictive model. The predictive model was displayed using a nomogram. We used the receiver operating characteristic curve, calibration curve, and clinical decision curve analysis (DCA) to evaluate model performance, and internal validation was assessed. Results: The predictive factors included in the prediction model were Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, emphysema, PaCO2, NT-pro-BNP, red blood cell (RBC) distribution width-standard deviation (RDW-SD), and neutrophil/lymphocyte ratio (NLR). The predictive model yielded an area under the curve (AUC) of 0.770 (95% confidence interval [CI], 0.719-0.820); in the internal validation, the AUC was 0.741 (95% CI, 0.659-0.823). The predictive model was well calibrated, and the DCA showed that the proposed nomogram had strong clinical applicability. Conclusion: This study showed that a simple nomogram could be used to calculate the risk of PH in patients with COPD which can be useful for the individualized clinical management of COPD patients who may be occur with PH. Further studies need to be confirmed by larger sample sizes and validated in the stable COPD population.

Incidence and prognostic value of pulmonary embolism in COVID-19: A systematic review and meta-analysis.

BACKGROUND: Pulmonary embolisms are frequently and prognostically in individuals infected by coronavirus disease 2019 (COVID-19); the incidence of pulmonary embolisms is varied across numerous studies. This study aimed to assess the pooled incidence of pulmonary embolic events and the prognostic value of such events in intensive care unit (ICU) admissions of patients with COVID-19. METHODS: The Cochrane Library, PubMed, and EmBase were systematically searched for eligible studies published on or before October 20, 2021. The pooled incidence of pulmonary embolism was calculated using the random-effects model. Moreover, the prognostic value was assessed by measuring the sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curve (AUC). RESULTS: Thirty-six studies involving 10,367 COVID-19 patients were selected for the final meta-analysis. The cumulative incidence of pulmonary embolism in patients with COVID-19 was 21% (95% confidence interval [95%CI]: 18-24%; P<0.001), and the incidence of pulmonary embolism in ICU and non-ICU patients was 26% (95%CI: 22-31%; P<0.001) and 17% (95%CI: 14-20%; P<0.001), respectively. The predictive role of pulmonary embolism in ICU admission was also assessed, and the sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.31 (95%CI: 0.21-0.42), 0.84 (95%CI: 0.75-0.90), 1.88 (95%CI: 1.45-2.45), 0.83 (95%CI: 0.75-0.91), 2.25 (95%CI: 1.64-3.08), and 0.61 (95%CI: 0.57-0.65), respectively. CONCLUSION: This study found that the incidence of pulmonary embolism was relatively high in COVID-19 patients, and the incidence of pulmonary embolism in ICU patients was higher than that in non-ICU patients.

Efficacy and Safety of Lianhua Qingke Tablets in the Treatment of Mild and Common-Type COVID-19: A Randomized, Controlled, Multicenter Clinical Study.

BACKGROUND: Lianhua Qingke (LH) tablets is an effective traditional Chinese medicine against various viral infections, especially in relieving coughing. However, its effects on COVID-19 are unknown. METHODS: To examine the therapeutic effectiveness of LH tablets in COVID-19 patients with mild and common types, a randomized, multicenter, controlled study was carried out. COVID-19 cases were randomized to undergo routine treatment with or without LH tablets (4 tablets, three times a day) for 14 days. The primary endpoints were the rate of achieving clinical symptom resolution and the corresponding time. RESULTS: There were 144 participants in the full analysis set (72 each in the LH and control groups). The LH group participants had elevated symptom alleviation rate at 14 days compared with control cases (FAS: 98.61% vs. 84.72%, p = 0.0026). In comparison with control group participants, the LH group participants had reduced median time to clinical symptom alleviation (median: 4 vs. 7 days, p < 0.0001). Higher resolution rates of coughing (98.44% vs. 84.51%, p = 0.0045) and expectoration (100% vs. 82.35%, p = 0.0268) were observed in the LH group. Times to recovery of fever (median: 2 vs. 3 days, p = 0.0007), coughing (median: 4 vs. 7 days, p < 0.0001), and expectoration (median: 3 vs. 6 days, p < 0.0001) were also notably shorter in the LH group. Moreover, the LH group had elevated improvement rates in chest computed tomography signs (FAS: 86.11% vs. 72.22%, p = 0.0402) and clinical cure at day 28 (FAS: 83.33% vs. 68.06%, p = 0.0326). However, no differences were found in the laboratory test and viral assay. Serious adverse events were not detected. CONCLUSION: These preliminary findings indicate LH tablets may be effective in symptomatic COVID-19, especially in relieving coughing. This trial was registered in Chinese Clinical Trial Registry (ChiCTR2100042069).

Asthma Management Using the Mobile Asthma Evaluation and Management System in China.

PURPOSE: As stated in the Global Initiative for Asthma, there are still some asthmatic patients who have not achieved asthma control. Mobile is a useful tool for asthma management. We aimed to compare the advantages of mobile management with traditional management in improving adherence and control of asthma. METHODS: In this prospective, multicentre, randomized, controlled and parallel-group study, we enrolled patients with poor adherence and uncontrolled asthma at 32 hospitals in 28 provinces in China. Patients were randomly assigned to the mobile management or traditional management groups for 12 months. The primary endpoint was the proportion of patients with good adherence (Medication Adherence Report Scale for Asthma [MARS-A] score ≥ 45) for 6 months. This study is registered at ClinicalTrials.gov (NCT02917174). RESULTS: Between April 2017 and April 2018, 923 patients were eligible for randomization (mobile group, n = 461; traditional group, n = 462). Dropout was 84 (18.2%) in the mobile management group and 113 (24.4%) patients in the traditional management group. The proportion of patients with good adherence was significantly higher in the mobile management group than in the traditional management group (66.0% vs. 58.99%, P = 0.048). The mobile management group showed higher mean MARS-A score (at 1, 6, 9, and 12 months) and asthma control test scores (at 6 and 9 months), and lower total lost rate to follow-up within 12 months than the traditional management group. CONCLUSIONS: Mobile asthma management can improve adherence and asthma control compared to traditional management. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02917174.

Effects of Crocin on CCL2/CCR2 Inflammatory Pathway in Monocrotaline-Induced Pulmonary Arterial Hypertension Rats.

Pulmonary arterial hypertension (PAH) is a malignant cardiopulmonary disease, in which pulmonary arterial remodeling is regarded as the prominent pathological feature. So far, the mechanism of PAH is still unclear, so its treatment remains a challenge. However, inflammation plays an important part in the occurrence and progression of PAH. It is well known that crocin has anti-inflammatory properties, so we investigated whether crocin could be a potential drug for the treatment of PAH rat models. Rats injected subcutaneously with monocrotaline (MCT) were treated with crocin via a gastric tube daily for four weeks. The results showed that crocin treatment significantly reduced the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) in the PAH rat models. Moreover, crocin treatment reduced the proliferation of pulmonary arteriole smooth muscle cells (PASMCs). In addition, crocin treatment not only relieved inflammatory cell infiltration and collagen fiber hyperplasia in the lung and right ventricle, but also decreased the expression of the CCL2/CCR2 inflammatory pathway in the lung of PAH rat models. Furthermore, crocin treatment reduced the inflammatory cytokines and oxidative stress responses. In summary, crocin may play a protective role in MCT-induced PAH rats by alleviating inflammatory response, improving pulmonary arterial remodeling, and preventing PAH. Therefore, crocin as a new treatment for PAH may be quite worthy of consideration.

Efficacy and Safety of Lianhuaqingwen Capsules for the Prevention of Coronavirus Disease 2019: A Prospective Open-Label Controlled Trial.

Coronavirus disease 2019 (COVID-19) has become a global pandemic. Community and close contact exposures continue to drive the COVID-19 pandemic. There is no confirmed effective treatment for suspected cases and close contacts. Lianhuaqingwen (LH) capsules, a repurposed Chinese herbal product that is currently on the market, have proven effective for influenza and COVID-19. To determine the safety and efficacy of LH capsules for the prevention of COVID-19, we conducted a prospective open-label controlled trial of LH capsules on subjects who had close contact with people infected with COVID-19. Subjects received LH capsules (4 capsules, three times daily) or the usual medical observation for 14 days. The primary endpoint was the rate of positive nucleic acid tests of nasal and pharyngeal swabs during the quarantine medical observation period. We included 1976 patients, including 1101 in the treatment group and 875 in the control group. The rate of positive nucleic acid tests in the treatment group was significantly lower than that in the control group (0.27% vs. 1.14%, respectively; mean difference: -0.87%; 95% CI: -1.83 to -0.13; p=0.0174) during the quarantine medical observation period (14 days). Among subjects with different close contact states, there was no significant difference in the rate of positive nucleic acid test results among close contacts in the treatment group and the control group (6.45% vs. 11.43%, respectively; p=0.6762). Among secondary close contacts, the rate of positive nucleic acid tests in the treatment group was significantly lower than that in the control group (0.09% vs. 0.71%, respectively; p=0.0485). No serious adverse events were reported. Taken together, and in light of the safety and effectiveness profiles, these results show that LH capsules can be considered to prevent the progression of COVID-19 after close contact with an infected person. This trial is registered with ChiCTR2100043012.

Comparison of invasive intubation and noninvasive mechanical ventilation in patients with chronic obstructive pulmonary disease and obstructive sleep apnoea syndrome.

OBJECTIVE: The concurrence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea syndrome (OSAS) is defined as overlap syndrome (OS), but investigations into predictors of OS in patients with COPD remain limited. Here, potential markers of OS in patients with COPD were investigated, and results of intubation were compared between patients with COPD only or OS. METHODS: This retrospective study included patients with COPD who were divided according to OS diagnosis: COPD only (COPD group) or OS (OS group). RESULTS: Among 206 patients with COPD, 120 were diagnosed with OS. Mean body mass index (BMI) was significantly higher in the OS versus COPD group (28.95 ± 2.96 versus 23.84 ± 4.06, respectively). Receiver operating characteristic curve analyses revealed that BMI was associated with OS (area under the curve, 0.835). The rate of invasive intubation within 48 h was lower in the OS versus COPD group (9.2% versus 20.9%, respectively), and the duration of noninvasive ventilation was longer in the OS versus COPD group. CONCLUSIONS: BMI may be a predictor of OS in patients with COPD. The duration of noninvasive ventilation was longer in patients with OS than in patients with COPD alone.