Dysregulated proteasome activity and steroid hormone biosynthesis are associated with mortality among patients with acute COVID-19.

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1-3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.

A combined immune and inflammatory indicator predict the prognosis of severe Pneumocystis jirovecii pneumonia patients: a 12-year, retrospective, observational cohort.

Persistent inflammatory damage and suppressed immune function play a crucial role in the pathogenesis and progression of the pneumocystis jirovecii pneumonia (PjP). Therefore, we aimed to investigate the correlation between the combined immune and inflammatory indicator: the neutrophil-to-lymphocyte ratio (NLR) and prognosis of non-human immunodeficiency virus (non-HIV) PjP.In the retrospective analysis conducted in ICUs at Beijing Chao-Yang Hospital, we examined data from 157 patients diagnosed with non-HIV PjP. Our findings reveal a concerning hospital mortality rate of 43.3%, with the 28-day mortality rate reaching 47.8%.Through multivariable logistic and Cox regression analyses, we established a significant association between elevated NLR levels and hospital mortality (adjusted odd ratio, 1.025; 95% CI, 1.008-1.043; p = 0.004) or 28-day mortality (adjusted hazard ratio, 1.026; 95% CI, 1.008-1.045; p = 0.005). Specifically, patients with an NLR exceeding 20.3 demonstrated markedly lower overall survival rates, underscoring the biomarker's predictive value for both hospital and 28-day mortality.In conclusion, non-HIV PjP patients in the ICU still have a high rate of mortality and a poor short-term prognosis after discharge. A high level of NLR was associated with an increased risk of hospital mortality and 28-day mortality.

Comparative Effectiveness of Mobile Health-Based Comprehensive Smoking Cessation Modalities and Traditional Clinic-Delivered Treatments - Beijing Municipality, China, May 2022 to April 2024.

What is already known about this topic?: Most Chinese smokers have not accessed professional help due to a lack of sufficient smoking cessation services. Mobile health (mHealth) can mitigate obstacles related to time and transportation, thereby providing effective support for smokers seeking to quit. What is added by this report?: This study offers real-world evidence supporting the effectiveness of mHealth-based comprehensive smoking cessation interventions. The findings indicate that these modalities can significantly enhance abstinence rates, albeit to a lesser extent compared to traditional clinic-based treatments. Adherence to the intervention was identified as a critical factor influencing the effectiveness of smoking cessation strategies. What are the implications for public health practice?: The mHealth-based comprehensive smoking cessation modalities, with or without mailing cessation medications, present a promising approach to enhancing access to and utilization of smoking cessation services. This strategy addresses the significant challenge of limited smoking cessation resources in China.

Utilizing EMR Data for Smoking Behavior Surveillance in Hospitalized Patients With Chronic Respiratory Diseases and Its Impact on Clinical Outcomes - Beijing Municipality, China, 2014-2023.

What is already known on this topic?: Smoking is the primary risk factor for a poor prognosis in chronic respiratory disease (CRD). Current tobacco surveillance efforts in China focus on the general population and do not adequately cover CRD patients. What is added by this report?: We employed electronic medical records (EMR) to track smoking habits in 28,334 hospitalized CRD patients at Beijing Chao-Yang Hospital. The rates of former and current smokers were 30.7% and 18.0%, respectively. Both former and current smokers exhibited an increased risk of respiratory symptoms and extended hospital stays. What are the implications for public health practice?: These results underscore the importance of implementing smoking monitoring and targeted cessation interventions for hospitalized patients with CRDs.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

Clinical Characteristics and Prognostic Predictors of Pneumocystis Jirovecii Pneumonia in Patients with and without Chronic Pulmonary Disease: A Retrospective Cohort Study.

Objective: Pneumocystis jirovecii pneumonia (PJP) is a severe respiratory infection caused by Pneumocystis jirovecii in immunocompromised hosts. The role of P. jirovecii colonization in the development or progression of various pulmonary diseases has been reported. Our aim was to explore serial change in serum biomarkers and the independent risk factors for mortality in patients with and without chronic pulmonary diseases who developed PJP. Methods: We performed a retrospective study to select patients with Pneumocystis jirovecii pneumonia between January 1, 2012, and December 31, 2021. Information regarding demographics, clinical characteristics, underlying diseases, laboratory tests, treatment, and outcomes was collected. Univariate and multivariate logistic regression analyses were used to identify independent predictors of in-hospital mortality. Results: A total of 167 patients diagnosed with PJP were included in the study: 53 in the CPD-PJP group and 114 in the NCPD-PJP group. The number of patients with PJP showed an increasing trend over the 10-year period. A similar trend was observed for in-hospital mortality. Independent risk factors associated with death in the NCPD-PJP group were procalcitonin level (adjusted OR 1.08, 95% CI 1.01-1.16, P=0.01), pneumothorax (adjusted OR 0.07, 95% CI 0.01-0.38, P=0.002), neutrophil count (adjusted OR 1.27, 95% CI 1.05-1.53, P=0.01) at 14 days, and hemoglobin level (adjusted OR 0.94, 95% CI 0.91-0.98; P=0.002) at 14 days after admission. The risk factor associated with death in the CPD-PJP group was neutrophil count (adjusted OR 1.19, 95% CI 0.99-1.43; P=0.05) at 14 days after admission. Conclusion: The risk factors for death were different between patients with PJP with and without chronic pulmonary disease. Early identification of these factors in patients with PJP and other underlying diseases may improve prognosis.

Tracking COPD exacerbation patterns and forecasting readmission risks utilizing electronic medical records.

INTRODUCTION: Accurate evaluation of exacerbation frequency is an essential part of COPD assessment. But relying on just the prior-year exacerbation history may not capture the full picture of risk given the inherent year-to-year fluctuations in exacerbation rates. This study aimed to evaluate the predictive performance of models incorporating the 3-year exacerbation history based on electronic medical record. MATERIALS AND METHODS: This retrospective cohort study included 86,501 COPD hospitalized patients in Beijing from 2008 to 2014. The annual frequency of COPD exacerbation hospitalizations over a 3-year period after the index hospitalization was calculated, with patients segmented into seven distinct exacerbation trajectory groups. Logistic regression was used to evaluate the predictive capability of the 3-year exacerbation history for exacerbation readmission in the fourth year. Predictors included age, sex, comorbidities, and exacerbation hospitalization in previous 1-3 years. Model performance was evaluated using area under the receiver operating characteristic curve (AUC). RESULTS: Of the studied patients, 56.5% were men, and the mean age (SD) was 73.8 (10.3) years. The overall readmission rate for COPD exacerbation was 0.31 per person-year, with only 3.8% of patients persistently readmitted over three consecutive years. The 3-year trajectory of exacerbation frequency was associated with exacerbation risk in the fourth year. Compared to just the prior year, the inclusion of a 3-year exacerbation hospitalization history notably improved prediction accuracy, with AUC elevating from 0.731 (0.724-0.739) to 0.786 (0.779-0.792). CONCLUSION: These results unveil the fluctuating nature of COPD exacerbation hospitalization frequency across years and demonstrate that integrating a more comprehensive 3-year exacerbation history significantly refines the prediction model for future risk, thus providing a more nuanced and actionable insight for clinical care.

Booster vaccines dose reduced mortality in hospitalized COVID-19 patients requiring oxygen supplementation: Evidence from the Beijing Omicron outbreak.

To assess the impact of vaccines on clinical outcomes among hospitalized COVID-19-infected patients requiring oxygen supplementation during the Beijing Omicron outbreak. We conducted a retrospective cohort study at Beijing Chaoyang Hospital, Capital Medical University, from November 15, 2022, to March 31, 2023. Vaccination statuses were categorized into 3 doses, 2 doses, and unvaccinated (0 dose). The primary outcome was 28-day all-cause mortality. Secondary outcomes included poor outcomes, intensive care unit admission, cardiovascular thromboembolism events, and hospital readmission. Among the included patients, 117 were 2 doses, 285 received booster doses, and 503 were unvaccinated. After propensity score inverse probability weighting, the 3 doses group showed a significantly lower 28-day all-cause mortality compared to the unvaccinated group (inverse probability of treatment weighting-adjusted HR: 0.64, 95% CI: 0.50-0.81). No significant difference was observed in all-cause mortality between the 2 doses and unvaccinated groups. No significant differences were observed in secondary outcome analyses when comparing the 3 doses or 2 doses group to the unvaccinated group. Subgroup analysis revealed significant benefits of booster vaccination in patients with shorter symptom duration, lower Charlson Comorbidity Index, and without immunosuppression status. Our study highlights the significant reduction in all-cause mortality among hospitalized Omicron-infected patients who received a third dose vaccine. These findings underscore the importance of prioritizing booster vaccinations, especially among the elderly. Further research is warranted to confirm and extend these observations.

Effect of Extended Prone Positioning in Intubated COVID-19 Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

INPLASY REGISTRATION NUMBER: INPLASY202390072.

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.

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.

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.

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.

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.

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.

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.