Two- and 3-year outcomes in convalescent individuals with COVID-19: A prospective cohort study.

As the long-term consequences of coronavirus disease 2019 (COVID-19) have not been defined, it is necessary to explore persistent symptoms, long-term respiratory impairment, and impact on quality of life over time in COVID-19 survivors. In this prospective cohort study, convalescent individuals diagnosed with COVID-19 were followed-up 2 and 3 years after discharge from hospital. Participants completed an in-person interview to assess persistent symptoms and underwent blood tests, pulmonary function tests, chest high-resolution computed tomography, and the 6-min walking test. There were 762 patients at the 2-year follow-up and 613 patients at the 3-year follow-up. The mean age was 60 years and 415 (54.5%) were men. At 3 years, 39.80% of the participants had at least one symptom; most frequently, fatigue, difficulty sleeping, joint pain, shortness of breath, muscle aches, and cough. The participants experienced different degrees of pulmonary function impairment, with decreased carbon monoxide diffusion capacity being the main feature; results remained relatively stable over the 2-3 years. Multiple logistic regression analysis demonstrated that female sex and smoking were independently associated with impaired diffusion capacity. A subgroup analysis based on disease severity was performed, indicating that there was no difference in other parameters of lung function except forced vital capacity at 3-year follow-up. Persistent radiographic abnormalities, most commonly fibrotic-like changes, were observed at both timepoints. At 3 years, patients had a significantly improved Mental Component Score compared with that at 2 years, with a lower percentage with anxiety. Our study indicated that symptoms and pulmonary abnormalities persisted in COVID-19 survivors at 3 years. Further studies are warranted to explore the long-term effects of COVID-19 and develop appropriate rehabilitation strategies.

Long-term outcomes of survivors with influenza A H1N1 virus-induced severe pneumonia and ARDS: a single-center prospective cohort study.

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

Nirmatrelvir-Ritonavir Reduced Mortality in Hospitalized Patients with COVID-19 During the Omicron Outbreak: Real-World Evidence from Beijing.

Objective: The efficacy of nirmatrelvir-ritonavir for hospitalized patients with COVID-19 has not been fully established. Methods: We conducted a retrospective analysis of hospitalized COVID-19 patients with high risk for disease progression at Beijing Chaoyang Hospital from October 15, 2022, to March 31, 2023. Patients ≥18 years old who were hospitalized with COVID-19 within 5 days of symptom onset were included. Baseline data were obtained from the routine electronic health record database of the hospital information system. Outcomes were monitored at 28 days via electronic medical record reviews or telephone interviews. Results: We identified 1120 patients hospitalized with COVID-19 during the study period. After exclusions, 167 nirmatrelvir-ritonavir users and 132 controls were included. 28-day all-cause mortality rate was 12.0% (20/167) in the nirmatrelvir-ritonavir group, versus 22.7% (30/132) in the control group (unadjusted log-rank p = 0.010; HR = 0.49, 95% confidence interval [CI] = 0.28-0.86, IPTW-adjusted HR = 0.58, 95% CI = 0.40-0.86). The 28-day disease progression rates did not differ between the two groups (unadjusted HR = 0.59, 95% CI = 0.34-1.02, IPTW-adjusted HR = 0.73, 95% CI = 0.50-1.06). Nirmatrelvir-ritonavir significantly reduced all-cause mortality and disease progression within 28 days among patients aged ≥65 years without ≥2 vaccine doses. Conclusion: We found significantly reduced all-cause mortality in the nirmatrelvir-ritonavir group, particularly in elderly patients who were incompletely vaccinated. Future randomized controlled studies are needed to validate our findings.

Association of blood eosinophils with corticosteroid treatment failure stratified by smoking status among inpatients with AECOPD.

BACKGROUND: Recent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been shown to affect corticosteroid response. Whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking has not been fully investigated so far. OBJECTIVES: This study aimed to assess whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking. METHODS: We included 3402 inpatients with AECOPD treated with corticosteroids at Beijing Chao-Yang Hospital from July 2013 to June 2021. Blood eosinophil counts were measured within 24 hours of admission. An eosinophil percentage ≥2% was considered as high eosinophilic. Smokers in this study were defined as current or former smokers. Treatment failure was defined as a worsening of AECOPD that led to adverse clinical outcomes or required further treatment or an extended hospital stay or hospitalisation following the exacerbation. Multivariate-adjusted logistic models were used to estimate the OR and 95% CI associated with treatment failure. RESULTS: There were 958 (28.2%) treatment failure events occurring. Patients with high eosinophils had a lower risk of treatment failure (OR 0.74, 95% CI 0.63 to 0.87) than patients with low eosinophils. Compared with never smoking and low eosinophilic group, the ORs for treatment failure were 0.70 (95% CI 0.52 to 0.96) for never smoking and high eosinophilic group, 0.82 (95% CI 0.64 to 1.05) for smoking and low eosinophilic group and 0.62 (95% CI 0.47 to 0.81) for smoking and high eosinophilic group. Furthermore, there was no significant interaction between eosinophils and smoking status in relation to treatment failure (p for interaction=0.73). Similar results were obtained from multiple secondary outcomes and subgroup analyses. CONCLUSION: Elevated blood eosinophils are associated with a lower rate of corticosteroid treatment failure, regardless of smoking status. Smoking does not modify the association between blood eosinophil level and corticosteroid treatment failure among inpatients with AECOPD.

Long-term trends and risk factors of tracheostomy and decannulation in patients with cervical spinal cord Injury.

STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate the risk factors of tracheostomy and decannulation after cervical spinal cord injury (CSCI) and their epidemiological changes over the past 8 years in Beijing Bo'ai Hospital, China Rehabilitation Research Center (CRRC), China. SETTING: Beijing Bo'ai Hospital, CRRC. METHODS: We reviewed 8 years of patient data (2013.1.1 to 2020.12.31) at CRRC, focusing on those hospitalized and diagnosed with CSCI. We analyzed changes in demographic and clinical data's trends. Logistic regression analysis was used to determine factors impacting tracheostomy and decannulation. RESULTS: Finally, 1641 CSCI patients met the inclusion criteria. Over the past 8 years, the proportion of tracheostomized patients with CSCI was 16.3%, and the proportion of successfully decannulated of tracheostomized patients with TCSCI was 77.9%. We found that Traumatic (OR = 1.8, 95% CI = 1.06, 3.22; p = 0.046), Motor level of injury (C5-C8) (OR = 0.32, 95% CI = -1.91,-0.34; p = 0.005), AIS = A/B/C (OR = 22.7/11.1/4.2, 95% CI = 12.16,42.26/5.74,21.56/2.23,7.89; p < 0.001/p < 0.001/p < 0.001), age > 56 (OR = 1.6, 95% CI = 1.04, 2.32; p = 0.031) were the risk factors for tracheostomy. By analyzing the risk factors of decannulation failure in tracheostomized patients with TCSCI through multivariable logistic regression, statistically significant differences were found in age > 45 (OR = 4.1, 95% CI = 1.44, 11.81; p = 0.008), complete injury (OR = 2.7, 95% CI = 1.26, 5.95; p = 0.011), facet dislocation (OR = 2.8, 95% CI = 1.13,7.07; p = 0.027). CONCLUSIONS: Recent years have witnessed shifts in the epidemiological characteristics of CSCI. Identifying the factors influencing tracheostomy and decannulation in CSCI can aid in improving patient prognosis.

MiR-150 levels are related to in-hospital mortality in non-HIV Pneumocystis pneumonia patients.

Pneumocystis pneumonia (PCP) is a common opportunistic infection that occurs in immunocompromised patients. Compared with HIV patients, PCP in non-HIV patients tends to follow up a more urgent course and poorer prognosis. Therefore, markers that could predict survival of PCP patients in non-HIV population are of great value. MiRNA-150 has been widely studied in many diseases since it has been identified as a vital regulator of immune cell differentiation and activation. We thus conduct this study aiming to evaluate the prognostic value of miR-150 level in non-HIV PCP. First, the expression levels of miR-150 were compared between PCP patients and healthy volunteers. The miR-150 levels in immune cells were also detected in PCP mouse models. Then the prognostic value of miR-150 was further assessed in another PCP population (n = 72). The expression levels of miR-150 were measured by reverse transcription real-time PCR (RT-PCR) technique. Our data demonstrated significantly decreased miR-150 expression levels in PCP patients and mouse models compared to controls. The miR-150 levels also decreased in various immune cells of PCP mouse models. With a cut-off value of 3.48, the area under the curve, sensitivity, specificity of miR-150 to predicate PCP mortality were 0.845, 68.2% and 96.0%, respectively. In conclusion, miR-150 expression value might serve as a potential biomarker to identify PCP patients at high risk of death.

Pneumocystis pneumonia (PCP) remains a fatal risk for immunosuppressed patients. MiR-150 takes part in immune regulation, and thus is involved in infection control. Our study indicated that the miR-150 expression may act as a potential biomarker for predicting mortality of PCP patients.

Comprehensive Nomograms Using Routine Biomarkers Beyond Eosinophil Levels: Enhancing Predictability of Corticosteroid Treatment Outcomes in AECOPD.

Purpose: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) exhibit heterogeneous responses to corticosteroid treatment. We aimed to determine whether combining eosinophil levels with other routine clinical indicators can enhance the predictability of corticosteroid treatment outcomes and to come up with a scoring system. Patients and Methods: Consecutive patients admitted with AECOPD receiving corticosteroid treatment between July 2013 and March 2022 at Beijing Chao-Yang Hospital were retrospectively analyzed. Data on patients' demographics, smoking status, hospitalization for AECOPD in the previous year, comorbidities, blood laboratory tests, in-hospital treatment and clinical outcomes were collected. Least absolute shrinkage and selection operator (LASSO) regression and backward logistic regression were used for predictor selection, and predictive nomograms were developed. The discrimination and calibration of the nomograms were assessed using the area under the receiver operating curve (AUC) and calibration plots. Internal validation was performed using the 500-bootstrap method, and clinical utility was evaluated using decision curve analysis (DCA). Results: Among the 3254 patients included, 804 (24.7%) had treatment failure. A nomogram of eosinophils, platelets, C-reactive protein (CRP), low density lipoprotein cholesterol, prognostic nutritional index (PNI), hospitalization for AECOPD in the previous year, ischemic heart diseases and chronic hepatic disease was developed to predict treatment failure for patients with a smoking history. For patients without a smoking history, a nomogram of CRP, PNI, ischemic heart diseases and chronic hepatic disease was developed. Although the AUCs of these two nomograms were only 0.644 and 0.647 respectively, they were significantly superior to predictions based solely on blood eosinophil levels. Conclusion: We developed easy-to-use comprehensive nomograms utilizing readily available clinical biomarkers related to inflammation, nutrition and immunity, offering modestly enhanced predictive value for treatment outcomes in corticosteroid-treated patients with AECOPD. Further investigations into novel biomarkers and additional patient data are imperative to optimize the predictive performance.

Encapsulated lignin-based slow-release manganese fertilizer with reduced cadmium accumulation in rice (Oryza sativa L.).

As an essential trace element for plant growth and development, manganese plays a crucial role in the uptake of the heavy metal cadmium by rice (Oryza sativa L.). In this study, we developed a novel slow-release manganese fertilizer named Mn@LNS-EL. Initially, lignin nanoparticles were derived from sodium lignosulfonate, and a one-step emulsification strategy was employed to prepare a water-in-oil-in-water (W/O/W) Pickering double emulsions. These double emulsions served as the template for interfacial polymerization of lignin nanoparticles and epichlorohydrin, resulting in the formation of microcapsule wall materials. Subsequently, manganese fertilizer (MnSO4) was successfully encapsulated within the microcapsules. Hydroponic experiments were conducted to investigate the effects of Mn@LNS-EL on rice growth and the cadmium and manganese contents in the roots and shoots of rice under cadmium stress conditions. The results revealed that the treatment with Mn@LNS-EL markedly alleviated the inhibitory effects of cadmium on rice growth, leading to notably lower cadmium levels in the rice roots and shoots compared to the specimens treated without manganese fertilizer. Specifically, there was a reduction of 37.9 % in the root cadmium content and a 17.1 % decrease in the shoot cadmium content. In conclusion, this study presents an innovative approach for the high-value utilization of lignin through effective encapsulation and slow-release mechanisms of trace-element fertilizers while offering a promising strategy for efficiently remediating cadmium pollution in rice.

The systemic immune-inflammation index is significantly associated with the severity of silicosis: a 9-year retrospective study in Beijing.

Background: Silicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis. Methods: In this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis. Results: A total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000-1.003, p < 0.001] after adjusting for all covariates. The best cutoff value of SII was 444.1. The results of the subgroup analysis also showed a significant correlation between SII level over 444.1 and the advanced stage of silicosis in groups stratified by gender, history of smoking, and duration of silica exposure. Moreover, our results showed a significant but weak negative correlation between the level of SII and some lung function parameters in silicosis. Conclusion: Higher SII is associated with the advanced stage of silicosis and impaired lung function. More long-term, large-scale studies are needed to confirm these findings.

Genomic Sequencing of Clinical Cupriavidus gilardii Isolates Revealed Their Diverse Antimicrobial Resistance Mechanisms.

Purpose: Cupriavidus gilardii is an emerging multidrug-resistant pathogen found in many environments and few clinical samples. The clinical infectiousness, pathogenicity, and resistance mechanisms of C. gilardii are still unclear due to the lack of clinical and sequencing data. We need to obtain insight into the clinical characteristics, virulence, and resistance mechanisms of C. gilardii. Patients and Methods: We isolated five C. gilardii isolates from hospitalized patients and carried out assay, culture and genome sequencing. We analyzed the genomic features of clinical C. gilardii isolates and took insight into their clinical characteristics, virulence, and resistance mechanisms. Results: These isolates were resistant to meropenem, gentamicin, and other antimicrobials due to intrinsic resistance genes. Furthermore, the sequencing results revealed the widespread presence of the MCR-5.1 gene in C. gilardii. The virulence magnitude of C. gilardii is closely correlated with the number of virulence factors they carry. Some C. gilardii strains can acquire resistance to levofloxacin through gyrA gene mutation during treatment. The diverse antimicrobial resistance mechanisms challenge the treatment of C. gilardii infections. Conclusion: We present the genomic characteristics of clinically isolated C. gilardii to improve (i) our understanding of this pathogen and (ii) treatment options.

Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia.

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited. METHODS: In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45+ cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models. RESULTS: Our results characterized the CD45+ cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C+ monocytes and interacted with effector CD4+ T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP. CONCLUSION: Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP's cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets.

Multi-omics analysis reveals overactive inflammation and dysregulated metabolism in severe community-acquired pneumonia patients.

BACKGROUND: Severe community-acquired pneumonia (S-CAP) is a public health threat, making it essential to identify novel biomarkers and investigate the underlying mechanisms of disease severity. METHODS: Here, we profiled host responses to S-CAP through proteomics analysis of plasma samples from a cohort of S-CAP patients, non-severe (NS)-CAP patients, diseases controls (DCs), and healthy controls (HCs). Then, typical differentially expressed proteins were then validated by ELISA in an independent cohort. Metabolomics analysis was further performed on both the cohort 1 and cohort 2. Then, the proteomic and metabolomic signatures were compared between the adult and child cohorts to explore the characteristics of severe pneumonia patients. RESULTS: There were clear differences between CAP patients and controls, as well as substantial differences between the S-CAP and NS-CAP. Pathway analysis of changes revealed excessive inflammation, suppressed immunity, and lipid metabolic disorders in S-CAP cases. Interestingly, comparing these signatures between the adult and child cohorts confirmed that overactive inflammation and dysregulated lipid metabolism were common features of S-CAP patients, independent of age. The change proportion of glycerophospholipids, glycerolipids, and sphingolipids were obviously different in the adult and child S-CAP cases. CONCLUSION: The plasma multi-omics profiling revealed that excessive inflammation, suppressed humoral immunity, and disordered metabolism are involved in S-CAP pathogenesis.

Predicting the death of patients with anti-melanoma differentiation-associated protein-5-positive dermatomyositis-associated interstitial lung disease: A systematic review and meta-analysis.

OBJECTIVES: To investigate the risk factors for death in anti-melanoma differentiation-associated protein-5-positive dermatomyositis-associated interstitial lung disease (ILD). METHODS: Studies were identified by searching PubMed, Embase, Web of Science, and Cochrane Library. We calculated pooled risk ratios (RRs) or standardized mean differences (SMDs) and 95% confidence intervals (CIs) using random-effects models. RESULTS: Twenty studies were selected. Factors that may increase death risk included older age (SMD: 0.62, 95% CI: 0.42-0.81), elevated Krebs von den Lungen-6 (SMD: 0.66, 95% CI: 0.47-0.86), lactate dehydrogenase (SMD: 0.87, 95% CI: 0.72-1.02), C-reactive protein (SMD: 0.62, 95% CI: 0.44-0.80), ferritin (SMD: 0.93, 95% CI: 0.71-1.15), creatine kinase (SMD: 0.28, 95% CI: 0.13-0.44), neutrophil (SMD: 0.34, 95% CI: 0.04-0.64), neutrophil-to-lymphocyte ratio (SMD: 0.52, 95% CI: 0.24-0.79), aspartate aminotransferase (SMD: 0.70, 95% CI: 0.45-0.94), shorter disease duration (SMD: -0.44, 95% CI: -0.67 to -0.21), rapidly progressive ILD (RR: 4.08, 95% CI: 3.01-5.54), fever (RR: 1.98, 95% CI: 1.46-2.69), dyspnoea (RR: 1.63, 95% CI: 1.32-2.02), and anti-Ro52 antibody positive (RR: 1.28, 95% CI: 1.11-1.49). Female (RR: 0.86, 95% CI: 0.78-0.94), increased albumin (SMD: -1.20, 95% CI: -1.76 to -0.64), lymphocyte (SMD: -0.49, 95% CI: -0.67 to -0.30), and arthralgia (RR: 0.53, 95% CI: 0.37-0.78) were protective factors. CONCLUSION: Older age, shorter disease duration, rapidly progressive ILD, fever, dyspnoea, anti-Ro52 antibody positive, and some inflammatory markers were risk factors for death in patients with anti-melanoma differentiation-associated protein-5-positive dermatomyositis-associated ILD.

Sedation and analgesia strategies for non-invasive mechanical ventilation: A systematic review and meta-analysis.

BACKGROUND: The use of sedative and analgesic drugs during non-invasive ventilation (NIV) in patients with acute respiratory failure (ARF) is controversial. OBJECTIVES: To assess the clinical effectiveness of sedative and analgesic medications used during NIV for patients with ARF to no sedation or analgesia. In addition, to investigate the characteristics of dexmedetomidine in comparison to other medications. METHODS: PubMed, Embase, Web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched. Mean differences (MDs) or pooled risk ratios (RRs) were computed using random-effects models. We applied the Cochrane risk-of-bias assessment tool 2.0 to assess the methodological quality of eligible studies and the GRADE approach to evaluate the evidence certainty. RESULTS: Twenty-one studies were selected. Whether in Group A (using sedative and analgesic drugs vs. nonuse) or Group B (using dexmedetomidine vs. other drugs), the rates of tracheal intubation and delirium, the length of NIV, and the length of stay in the intensive care unit (ICU LOS) all decreased in both experimental groups (P < 0.05). And there were no significant differences in all-cause mortality and the incidence of hypotension between the two groups (P > 0.05), while both Group A and Group B's experimental groups had greater incidences of bradycardia. CONCLUSIONS: Administering sedative and analgesic medications during NIV can reduce the risk of tracheal intubation and delirium. Additionally, dexmedetomidine outperformed other sedative medications in terms of these clinical outcomes, making it the better option when closely monitoring patients' vital signs.

Phospholipase PLCE1 Promotes Transcription and Phosphorylation of MCM7 to Drive Tumor Progression in Esophageal Cancer.

Phospholipase C epsilon 1 (PLCE1) is a well-established susceptibility gene for esophageal squamous cell carcinoma (ESCC). Identification of the underlying mechanism(s) regulated by PLCE1 could lead to a better understanding of ESCC tumorigenesis. In this study, we found that PLCE1 enhances tumor progression by regulating the replicative helicase MCM7 via two pathways. PLCE1 activated PKCα-mediated phosphorylation of E2F1, which led to the transcriptional activation of MCM7 and miR-106b-5p. The increased expression of miR-106b-5p, located in intron 13 of MCM7, suppressed autophagy and apoptosis by targeting Beclin-1 and RBL2, respectively. Moreover, MCM7 cooperated with the miR-106b-25 cluster to promote PLCE1-dependent cell-cycle progression both in vivo and in vitro. In addition, PLCE1 potentiated the phosphorylation of MCM7 at six threonine residues by the atypical kinase RIOK2, which promoted MCM complex assembly, chromatin loading, and cell-cycle progression. Inhibition of PLCE1 or RIOK2 hampered MCM7-mediated DNA replication, resulting in G1-S arrest. Furthermore, MCM7 overexpression in ESCC correlated with poor patient survival. Overall, these findings provide insights into the role of PLCE1 as an oncogenic regulator, a promising prognostic biomarker, and a potential therapeutic target in ESCC. SIGNIFICANCE: PLCE1 promotes tumor progression in ESCC by activating PKCα-mediated phosphorylation of E2F1 to upregulate MCM7 and miR-106b-5p expression and by potentiating MCM7 phosphorylation by RIOK2.

The Relationship of Fractional Exhaled Nitric Oxide in Patients with AECOPD.

Objective: To identify the relationship between patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their fractional-exhaled nitric oxide (FeNO) levels. Methods: Patients diagnosed with AECOPD in the respiratory department of Beijing Chaoyang Hospital from June 2017 to August 2019 were recorded. The demographic data, FeNO value, peripheral blood eosinophil count, number of acute exacerbations in the past year, pulmonary function test, use of inhaled glucocorticoids (ICS) and other data were collected and analyzed. FeNO was measured again three months after discharge, the participants were assessed to determine if the stable period criteria were met. Results: A total of 214 patients met the requirements of this study. 25ppb for FeNO was used as the cutoff for further analysis. The proportion of males, number of acute exacerbations in the past year, number of ICS users, leukocyte count and eosinophil count in the high FeNO-level group was significantly higher than that in the low-level group (P < 0.05). The results showed that the number of acute exacerbations in the past year, number of ICS users, and eosinophil count were statistically significant in the model (P < 0.05). The study also showed that the level of FeNO in the acute exacerbation phase was significantly higher than that in the stable phase. The ROC curve that the area under the curve used by FeNO to predict ICS used is 0.631 (95% CI: 0.526-0.736), and the corresponding P value is 0.022. Conclusion: FeNO is closely related to activated T2 inflammation and eosinophil count in COPD patients. The FeNO levels can be used as an index to evaluate the severity of COPD and predict the recovery of activity after ICS treatment. FeNO can predict the use of ICS and is a beneficial supplement to eosinophils.

The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation.

Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-ß production, allowing persistent viral load and exacerbated inflammation. While the SARS-CoV-2 nucleocapsid (N) protein has been implicated in inhibiting innate immunity by interfering with IFN-ß signaling, the specific underlying mechanism still needs further investigation for a comprehensive understanding. This study reveals that the SARS-CoV-2 N protein enhances interaction between the human SUMO-conjugating enzyme UBC9 and MAVS. Increased MAVS-UBC9 interaction leads to enhanced SUMOylation of MAVS, inhibiting its ubiquitination, resulting in the inhibition of phosphorylation events involving IKKα, TBK1, and IRF3, thus disrupting IFN-ß signaling. This study highlights the role of the N protein of SARS-CoV-2 in modulating the innate immune response by affecting the MAVS SUMOylation and ubiquitination processes, leading to inhibition of the IFN-ß signaling pathway. These findings shed light on the complex mechanisms utilized by SARS-CoV-2 to manipulate the host's antiviral defenses and provide potential insights for developing targeted therapeutic strategies against severe COVID-19.

Double trouble: The interaction of PM2.5 and O3 on respiratory hospital admissions.

The co-occurrence of fine particulate matter (PM2.5) and ozone (O3) pollution during the warm season has become a growing public health concern. The interaction between PM2.5 and O3 and its contribution to disease burden associated with co-pollution has not been thoroughly examined. We collected data on hospital admissions for respiratory diseases from a city-wide hospital discharge database in Beijing between 2013 and 2019. City-wide 24-h mean PM2.5 and daily maximum 8-h mean O3 were averaged from 35 monitoring stations across Beijing. Conditional Poisson regression was employed to estimate the interaction between warm-season PM2.5 and O3 on respiratory admissions. A model incorporating a tensor product term was used to fit the non-linear interaction and estimate the number of respiratory admissions attributable to PM2.5 and O3 pollution. From January 18, 2013 to December 31, 2019, 1,191,308 respiratory admissions were recorded. We observed multiplicative interactions between warm-season PM2.5 and O3 on upper respiratory infections (P = 0.004), pneumonia (P = 0.002), chronic obstructive pulmonary disease (P = 0.041), and total respiratory disease (P < 0.001). PM2.5-O3 co-pollution during warm season exhibited a super-additive effect on respiratory admissions, with a relative excess risk due to interaction of 1.65% (95%CI: 0.46%-2.84%). There was a non-linear pattern of the synergistic effect between PM2.5 and O3 on respiratory admissions. Based on the World Health Organization global air quality guidelines, 12,421 respiratory admissions would be reduced if both daily PM2.5 and O3 concentrations had not exceeded the target (PM2.5 15 µg/m3, O3 100 µg/m3). The number of respiratory admissions attributable to either PM2.5 or O3 pollution decreased by 48.7% from 2013 to 2019. Prioritizing O3 control during the warm season is a cost-effective strategy for Beijing. These findings underscore the significance of concurrently addressing both PM2.5 pollution and O3 pollution during the warm season to alleviate the burden of respiratory diseases.

A WeChat mini-program-based approach to smoking cessation behavioral interventions: Development and preliminary evaluation in a single-arm trial.

Objective: This study sought to develop a WeChat mini-program for smoking cessation behavioral interventions (named the WQ mini-program) and evaluate its usability, acceptability, and preliminary efficacy among Chinese smokers. Methods: The WQ mini-program was designed based on behavioral change theories and clinical practice guidelines, and clinical smoking cessation experts participated in the development process. Fifty Chinese smokers and five software experts were involved in a single-arm trial. Smokers were asked to use the WQ mini-program at least once a day for 4 weeks and to complete a weekly online follow-up questionnaire. Software experts were asked to complete an online follow-up questionnaire after using all functions of the WQ mini-program. Primary outcomes were usability and acceptability of and satisfaction with the mini-program tested by the System Usability Scale (SUS) and the Mobile App Rating Scale (MARS). Self-reported 7-day point prevalence abstinence (PPA) was used to evaluate its preliminary efficacy for smoking cessation. Optimization suggestions for the mini-program were collected from all participants through an open-ended question at the last follow-up and were analyzed by thematic analysis. Results: The mean SUS and MARS total scores for the WQ mini-program as evaluated by smokers were 82.1 ± 13.8 and 84.5 ± 3.3 and by software experts were 4.21 ± 0.32 and 4.27 ± 0.15, respectively. Most smokers reported being willing to recommend this mini-program to other smokers (85.4%) and would continue to use it (95.8%). The mean satisfaction score for the mini-program was 4.23 ± 0.69 (out of 5 points) among smokers. Self-reported 7-day PPA among smokers at the 4-week follow-up was 50% (25/50). Conclusions: This study demonstrated that the WQ mini-program would be a feasible and potentially effective method to encourage Chinese smokers to quit smoking. However, future research is needed to confirm its efficacy through a randomized controlled trial.