The role of serum sodium in poor prognosis evaluation of pulmonary hypertension associated with left heart disease.

BACKGROUND: Previous studies have shown that hyponatremia was strongly associated with a poor prognosis of type 1 pulmonary hypertension, and our team's antecedent studies found that low serum sodium was associated with the severity and the length of hospitalization of pulmonary hypertension associated with left ventricular disease (PH-LHD). However, the relationship between serum sodium and the prognosis of PH-LHD remains unclear. This study aims to determine the clinical value of serum sodium in evaluating poor prognosis in patients with PH-LHD. METHODS: We successfully followed 716 patients with PH-LHD. Kaplan-Meier was used to plot survival in PH-LHD patients with different serum sodium levels. The effect of serum sodium on poor prognosis was analyzed using a Cox proportional risk model. The trends between patients serum sodium and survival were visualized by restricted cubic spline (RCS). RESULTS: The survival rates at 1, 2, 3 and 4 years were 52%, 41%, 31% and 31% for the patients with hyponatremia associated with PH-LHD and 71%, 71%, 71% and 54% for the patients with hypernatremia, respectively. The observed mortality rate in the hyponatremia and hypernatremia groups surpassed that of the normonatremic group. The adjusted risks of death (risk ratio) for patients with hyponatremia and hypernatremia were found to be 2.044 and 1.877. Furthermore, the restricted cubic spline demonstrated an L-shaped correlation between serum sodium and all-cause mortality in patients with PH-LHD. CONCLUSIONS: Abnormal serum sodium level is strongly associated with poor prognosis in PH-LHD. Serum sodium may play an important pathogenic role in PH-LHD occurrence and could be used as a marker to assess the survival in patients.

Associations between air pollution and the onset of acute exacerbations of chronic obstructive pulmonary disease: A time-stratified case-crossover study in China.

BACKGROUND: Associations between air pollution and the acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have been established primarily in time-series studies in which exposure and case data were at the aggregate level, limiting the identification of susceptible populations. RESEARCH QUESTION: Are air pollutants associated with the onset of AECOPD in China? Who is more susceptible to the effects of air pollutants? STUDY DESIGN AND METHODS: AECOPD data were obtained from the Acute Exacerbation of Chronic Obstructive Pulmonary Disease Registry study and air pollution data were assigned to individuals based on their residential address. We adopted a time-stratified case-crossover study design combined with conditional logistic regression models to estimate the associations between six air pollutants and AECOPD. Stratified analyses were performed by individual characteristics, disease severity, COPD types, and the season of exacerbations. RESULTS: A total of 5,746 patients were finally included. At a 2-day lag, for each interquartile range increase in PM2.5 and PM10 concentrations, odds ratios for AECOPD were 1.054 (95% CI: 1.012, 1.097) and 1.050 (95% CI: 1.009, 1.092), respectively. The associations were more pronounced in participants who were aged < 65 years, had experienced at least one severe AECOPD in the past year, were first diagnosed with COPD between the ages of 20 and 50, and experienced AECOPD in the cool seasons. By contrast, significant associations for NO2, SO2, and CO lost significance when excluding cases collected before 2020 or with larger distance from the monitoring station, and no significant association was observed for O3. INTERPRETATION: This study provides robust evidence that short-term exposure to PM2.5 and PM10 was associated with higher odds of AECOPD onset. Individuals who are young, have severe COPD or young COPD, and experience an exacerbation during the cooler seasons may be particularly susceptible. CLINICAL TRIAL REGISTRATION NUMBER: NCT2657525 (ClinicalTrials.gov).

Predictive Value of Smoking Index Combined with NT-proBNP for Patients with Pulmonary Hypertension Due to Chronic Lung Disease: A Retrospective Study.

Purpose: Smoking is a major risk factor for the group 3 PH. NT-proBNP is a biomarker for risk stratification in PH. This study aims to investigate the effects of smoking status and smoking index (SI) on group 3 PH and to evaluate the value of SI and SI combined with NT-proBNP in early diagnosis and prediction of disease severity. Patients and Methods: Four hundred patients with group 3 PH at the First Hospital of Shanxi Medical University between January 2020 and December 2021 were enrolled and divided into two groups: mild (30 mmHg ≤ pulmonary artery systolic pressure (PASP)≤50 mmHg) and non-mild (PASP >50 mmHg). The effect of smoking on group 3 PH was analyzed using univariate analysis, and logistic analysis was conducted to evaluate the risk of group 3 PH according to smoking status and SI. Spearman correlation coefficient was used to test the correlation between SI and the index of group 3 PH severity. The predictive value of SI was evaluated using a receiver operating characteristic (ROC) curve. Results: Correlation and logistic analyses showed that SI was associated with PH severity. Smoking status (P=0.009) and SI (P=0.039) were independent risk factors for non-mild group 3 PH, and ROC showed that the predictive value of SI (AUC:0.596) for non-mild PH was better than that of the recognized pro-brain natriuretic peptide (NT-proBNP) (AUC:0.586). SI can be used as a single predictive marker. SI and NT-proBNP can be formulated as prediction models for screening non-mild clinical cases (AUC:0.628). Conclusion: SI is a potentially ideal non-invasive predictive marker for group 3 PH. SI and NT-proBNP could be used to develop a prediction model for screening non-mild PH cases. This can greatly improve the predictive specificity of the established PH marker, NT-proBNP.

A Novel Frameshift Variant of the ELF4 Gene in a Patient with Autoinflammatory Disease: Clinical Features, Transcriptomic Profiling and Functional Studies.

We described the diagnosis and treatment of a patient with autoinflammatory disease, named "Deficiency in ELF4, X-linked (DEX)". A novel ELF4 variant was discovered and its pathogenic mechanism was elucidated. The data about clinical, laboratory and endoscopic features, treatment, and follow-up of a patient with DEX were analyzed. Whole exome sequencing and Sanger sequencing were performed to identify potential pathogenic variants. The mRNA and protein levels of ELF4 were analyzed by qPCR and Western blotting, respectively. The association of ELF4 frameshift variant with nonsense-mediated mRNA decay (NMD) in the pathogenesis DEX was examined. Moreover, RNA-seq was performed to identify the key molecular events triggered by ELF4 variant. The relationship between ELF4 and IFN-ß activity was validated using a dual-luciferase reporter assay and a ChIP-qPCR assay. An 11-year-old boy presented with a Behçet's-like phenotype. The laboratory abnormality was the most obvious in elevated inflammatory indicators. Endoscopy revealed multiple ileocecal ulcers. Intestinal histopathology showed inflammatory cell infiltrations. The patient was treated with long-term immunosuppressant and TNF-α blocker (adalimumab), which reaped an excellent response over 16 months of follow-up. Genetic analysis identified a maternal hemizygote frameshift variant (c.1022del, p.Q341Rfs*30) in ELF4 gene in the proband. The novel variant decreased the mRNA level of ELF4 via the NMD pathway. Mechanistically, insufficient expression of ELF4 disturbed the immune system, leading to immunological disorders and pathogen susceptibility, and disrupted ELF4-activating IFN-ß responses. This analysis detailed the clinical characteristics of a Chinese patient with DEX who harbored a novel ELF4 frameshift variant. For the first time, we used patient-derived cells and carried out transcriptomic analysis to delve into the mechanism of ELF4 variant in DEX.

Developing and validating prediction models for severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO) in China: a prospective observational study.

BACKGROUND: There is a lack of individualised prediction models for patients hospitalised with chronic obstructive pulmonary disease (COPD) for clinical practice. We developed and validated prediction models of severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO). METHODS: Data were obtained from the Acute Exacerbations of Chronic Obstructive Pulmonary Disease Inpatient Registry study (NCT02657525) in China. Cause-specific hazard models were used to estimate coefficients. C-statistic was used to evaluate the discrimination. Slope and intercept were used to evaluate the calibration and used for model adjustment. Models were validated internally by 10-fold cross-validation and externally using data from different regions. Risk-stratified scoring scales and nomograms were provided. The discrimination ability of the SERCO model was compared with the exacerbation history in the previous year. RESULTS: Two sets with 2196 and 1869 patients from different geographical regions were used for model development and external validation. The 12-month severe exacerbations cumulative incidence rates were 11.55% (95% CI 10.06% to 13.16%) in development cohorts and 12.30% (95% CI 10.67% to 14.05%) in validation cohorts. The COPD-specific readmission incidence rates were 11.31% (95% CI 9.83% to 12.91%) and 12.26% (95% CI 10.63% to 14.02%), respectively. Demographic characteristics, medical history, comorbidities, drug usage, Global Initiative for Chronic Obstructive Lung Disease stage and interactions were included as predictors. C-indexes for severe exacerbations were 77.3 (95% CI 70.7 to 83.9), 76.5 (95% CI 72.6 to 80.4) and 74.7 (95% CI 71.2 to 78.2) at 1, 6 and 12 months. The corresponding values for readmissions were 77.1 (95% CI 70.1 to 84.0), 76.3 (95% CI 72.3 to 80.4) and 74.5 (95% CI 71.0 to 78.0). The SERCO model was consistently discriminative and accurate with C-indexes in the derivation and internal validation groups. In external validation, the C-indexes were relatively lower at 60-70 levels. The SERCO model discriminated outcomes better than prior severe exacerbation history. The slope and intercept after adjustment showed close agreement between predicted and observed risks. However, in external validation, the models may overestimate the risk in higher-risk groups. The model-driven risk groups showed significant disparities in prognosis. CONCLUSION: The SERCO model provides individual predictions for severe exacerbation and COPD-specific readmission risk, which enables identifying high-risk patients and implementing personalised preventive intervention for patients with COPD.

Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Respiratory Microbiome Profiles Associated With Distinct Inflammatory Phenotype and Clinical Indexes in Chronic Obstructive Pulmonary Disease.

Introduction/Objective: Respiratory microbiome studies have fostered our understanding of the various phenotypes and endotypes of heterogeneous chronic obstructive pulmonary disease (COPD). This study aimed to identify microbiome-driven clusters that reflect the clinical features and dominant microbiota of COPD. Methods: This cross-sectional study included 32 patients with stable COPD between December 2019 and December 2020 from the outpatient clinic of the China-Japan Friendship Hospital. Sputum samples were tested for 16S rRNA. Patients were classified according to the species level using an unsupervised clustering method to compare the inflammatory phenotypes of 2 clusters and analyze the correlation between the main bacteria and clinical indicators in each cluster. Patients were further divided into 2 clusters according to microorganisms. Results: Neutrophils in cluster 1 were significantly increased compared with cluster 2. Cluster 1 was predominantly Bacteroides, while cluster 2 was dominated by Prevotella and Fusobacterium at the genus level. Fusobacterium was negatively correlated with the COPD Assessment Test (CAT) score, and Bacteroides were positively correlated with the number of acute exacerbations of COPD. Conclusion: This study found that differential flora was negatively associated with CAT scores and the number of acute exacerbations of COPD. This microbiome-driven, unbiased clustering method for COPD can help identify new endotype-related COPD phenotypes.

Impact of diabetes itself and glycemic control status on tuberculosis.

Objectives: To explore the impact of diabetes itself and glycemic control status on tuberculosis (TB). Methods: A total of 3393 patients with TB and diabetes mellitus (DM) who were hospitalized in the Public Health Clinical Center of Chengdu from January 1, 2019, to December 31, 2021, were retrospectively included and divided into three groups according to baseline glycemic control status: two groups according to glycemic status at discharge, two groups according to cavity occurrence, three groups according to sputum results, and three groups according to lesion location. The influencing factors and the differences in cavity occurrence, sputum positivity and lesion location among different glycemic control groups or between different glycemic status groups were analyzed. Results: In this TB with DM cohort, most of the subjects were male, with a male to female ratio of 4.54:1, most of them were 45-59 years old, with an average age of 57.44 ± 13.22 years old. Among them, 16.8% (569/3393) had cavities, 52.2% (1770/3393) were sputum positive, 30.4% (1030/3393) had simple intrapulmonary lesions, 68.1% (2311/3393) had both intra and extrapulmonary lesions, only 15.8% (537/3393) had good glycemic control,16.0% (542/3393) and 68.2% (2314/3393) had fair and poor glycemic control, respectively. Compared with the non-cavity group, the sputum-negative group and the extrapulmonary lesion group, the cavity group, sputum-positive group, intrapulmonary lesion group and the intra and extrapulmonary lesion group all had higher fasting plasma glucose (FPG) and glycosylated hemoglobin A 1c (HbA1c) and lower good glycemic control rates at admission (all P<0.001). Another aspect, compared with the good glycemic control group, the poor glycemic control group had a higher cavity occurrence rate, sputum positive rate, and greater proportion of intrapulmonary lesions. Moreover, FPG and HbA1c levels and poor glycemic control were significantly positively correlated with cavity occurrence, sputum positivity, and intrapulmonary lesions and were the main risk factors for TB disease progression. On the other hand, cavity occurrence, sputum positivity, and intrapulmonary lesions were also main risk factors for hyperglycemia and poor glycemic control. Conclusion: Diabetes itself and glycemic control status could impact TB disease. Good glycemic control throughout the whole process is necessary for patients with TB and DM to reduce cavity occurrence and promote sputum negative conversion and lesion absorption.

How immune breakthroughs could slow disease progression and improve prognosis in COVID-19 patients: a retrospective study.

Background: Previous infections and vaccinations have produced preexisting immunity, which differs from primary infection in the organism immune response and may lead to different disease severities and prognoses when reinfected. Objectives: The purpose of this retrospective cohort study was to investigate the impact of immune breakthroughs on disease progression and prognosis in patients with COVID-19. Methods: A retrospective cohort study was conducted on 1513 COVID-19 patients in Chengdu Public Health Clinical Medical Center from January 2020 to November 2022. All patients were divided into the no immunity group (primary infection and unvaccinated, n=1102) and the immune breakthrough group (previous infection or vaccination, n=411). The immune breakthrough group was further divided into the natural immunity subgroup (n=73), the acquired immunity subgroup (n=322) and the mixed immunity subgroup (n=16). The differences in clinical and outcome data and T lymphocyte subsets and antibody levels between two groups or between three subgroups were compared by ANOVA, t test and chi-square test, and the relationship between T lymphocyte subsets and antibody levels and the disease progression and prognosis of COVID-19 patients was assessed by univariate analysis and logistic regression analysis. Results: The total critical rate and the total mortality rate were 2.11% and 0.53%, respectively. The immune breakthrough rate was 27.16%. In the no immunity group, the critical rate and the mortality rate were all higher, and the coronavirus negative conversion time was longer than those in the immune breakthrough group. The differences in the critical rate and the coronavirus negative conversion time between the two groups were all statistically significant (3.72% vs. 0.24%, 14.17 vs. 11.90 days, all p<0.001). In addition, in the no immunity group, although lymphocyte counts and T subsets at admission were higher, all of them decreased consistently and significantly and were significantly lower than those in the immune breakthrough group at the same time from the first week to the fourth week after admission (all p<0.01). The total antibody levels and specific Immunoglobulin G (IgG) levels increased gradually and were always significantly lower than those in the immune breakthrough group at the same time from admission to the fourth week after admission (all p<0.001). Moreover, in the natural immunity subgroup, lymphocyte counts and T subsets at admission were the highest, and total antibody levels and specific IgG levels at admission were the lowest. Then, all of them decreased significantly and were the lowest among the three subgroups at the same time from admission to one month after admission (total antibody: from 546.07 to 158.89, IgG: from 6.00 to 3.95) (all p<0.001). Those in the mixed immunity subgroup were followed by those in the acquired immunity subgroup. While lymphocyte counts and T subsets in these two subgroups and total antibody levels (from 830.84 to 1008.21) and specific IgG levels (from 6.23 to 7.51) in the acquired immunity subgroup increased gradually, total antibody levels (from 1100.82 to 908.58) and specific IgG levels (from 7.14 to 6.58) in the mixed immunity subgroup decreased gradually. Furthermore, T lymphocyte subsets and antibody levels were negatively related to disease severity, prognosis and coronavirus negative conversion time. The total antibody, specific IgM and IgG levels showed good utility for predicting critical COVID-19 patients and dead COVID-19 patients. Conclusion: Among patients with COVID-19 patients, immune breakthroughs resulting from previous infection or vaccination, could decelerate disease progression and enhance prognosis by expediting host cellular and humoral immunity to accelerate virus clearance, especially in individuals who have been vaccinated and previously infected. Clinical trial registry: Chinese Clinical Trial Register ChiCTR2000034563.

Associations of medication regimen complexity with medication adherence and clinical outcomes in patients with chronic obstructive pulmonary disease: a prospective study.

BACKGROUND: High medication burdens are common in patients with chronic obstructive pulmonary disease (COPD). This study aimed to explore the associations of medication regimen complexity index (MRCI) with medication adherence and clinical outcomes among patients with acute exacerbations of COPD (AECOPD) after hospital discharge. METHODS: Data were obtained from a nationwide cohort study of inpatients with AECOPD in China. MRCI scores were calculated using the medication list 30 days after discharge and separated into COPD-specific and non-COPD MRCI scores. Medication adherence was measured by the withdrawal rate of COPD or inhaled long-acting bronchodilators 6 months after discharge. Clinical outcomes included re-exacerbations and COPD-related readmissions during the 30-day to 6-month follow-up period. The associations of MRCI with medication withdrawal and clinical outcomes were evaluated using univariate and multivariate logistic regressions. Potential covariates included sociodemographic factors, year of COPD diagnosis, post-bronchodilator percentage predicted forced expiratory volume in 1 s, mMRC score, CAT score, and comorbidities. RESULTS: Among the 2853 patients included, the median total MRCI score was 7 [interquartile range (IQR), 7-13]. A high MRCI score (>7) was presented in 1316 patients (46.1%). Of the MRCI score, 91% were COPD specific. The withdrawal rates of the COPD and inhaled long-acting bronchodilators were 24.2% and 24.4%, respectively. Re-exacerbation and COPD-related readmission rates were 10.2% and 7.5%, respectively. After adjusting for covariates, patients with high total MRCI scores were less likely to discontinue COPD drugs [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.52-0.74] and inhaled long-acting bronchodilators (OR, 0.68; 95%CI, 0.57-0.81); conversely, these patients were more likely to experience re-exacerbation (OR, 1.64; 95% CI, 1.27-2.11) and readmission (OR, 1.57; 95% CI, 1.17-2.10). CONCLUSION: MRCI scores were relatively low among post-hospitalized patients with AECOPD in China. Higher MRCI scores were positively associated with adherence to COPD or inhaled medications, and risk of re-exacerbation and readmission. REGISTRATION: ClinicalTrials.gov identifier: NCT02657525.

Re-exacerbation within 30 days of discharge is associated with poor prognosis in the following year among patients hospitalised with exacerbation of chronic obstructive pulmonary disease: a clinical cohort study.

BACKGROUND: Exacerbation of chronic obstructive pulmonary disease (ECOPD) is a complex phenomenon, with marked heterogeneity in the aetiology, pathophysiology and clinical manifestations. This study aimed to evaluate the clinical characteristics and long-term outcomes of patients with 30-day exacerbation among those hospitalised with ECOPD in China. METHODS: Data from the Acute Exacerbations of Chronic Obstructive Pulmonary Disease Inpatient Registry were used in this study. The patients were divided into re-event and non-event groups based on the incidence of re-exacerbation within 30 days of discharge. Exacerbation, severe exacerbation and all-cause readmissions in the following 12 months were the outcomes of interest. The cumulative incidence rates and incidence densities were calculated. Multivariate hazard function models were used to determine the association between 30-day re-exacerbation and the long-term outcomes after accounting for the competing risk of death. RESULTS: Re-exacerbation within 30 days of discharge was observed in 4.9% (n=242) of the patients (n=4963). The cumulative incidence rates and incidence densities of exacerbation, severe exacerbation and all-cause readmissions in the event group were significantly higher than those in the non-event group. After adjustment, re-exacerbation within 30 days of discharge was associated with increased risks of exacerbation, severe exacerbation and all-cause readmissions in the following 12 months (adjusted HR: 3.85 (95% CI: 3.09 to 4.80), 3.46 (2.66 to 4.50) and 3.28 (2.52 to 4.25) accordingly). CONCLUSION: Re-exacerbation of COPD within 30 days of discharge is a significant predictor of long-term prognosis. In clinical practice, short-term re-exacerbation is a significant clinical phenotype of ECOPD that requires careful management at the earliest.

Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China: Findings from the real-world data.

BACKGROUND: Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease (COPD). However, limited information is available on vaccination coverage among patients with acute exacerbations of COPD (AECOPD) in China. This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD. METHODS: Baseline data from a national, multicenter, hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed. The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years. To ensure national representativeness, rates were weighted according to the distribution of hospital levels and types enrolled in this study. Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors. The independent variables included the region and hospital features where the participants were located, sociodemographic characteristics (age, sex, rural/urban residence, education, etc.), and clinical indicators (COPD disease history, lung function parameters, comorbidities, etc.). The treatment profiles of the vaccinated and unvaccinated participants were compared. RESULTS: Of 6949 eligible participants, the weighted rates of influenza/pneumococcal, influenza, and pneumococcal vaccination were 2.72% (95% confidence interval [CI]: 2.34-3.10%), 2.09% (95% CI: 1.76-2.43%), and 1.25% (95% CI: 0.99-1.51%), respectively. In multivariable models, age ≥60 years (60-69 years, odds ratio [OR]: 1.90, 95% CI: 1.11-3.25; ≥80 years, OR: 2.00, 95% CI: 1.06-3.78), geographical regions (Northern China relative to Eastern China, OR: 5.09, 95% CI: 1.96-13.21), urban residence (OR: 1.69, 95% CI: 1.07-2.66), a higher education level (junior high school, OR: 1.77, 95% CI: 1.21-2.58; senior high school or above, OR: 2.61, 95% CI: 1.69-4.03), former smoking (OR: 1.79, 95% CI: 1.15-2.79), and regular inhaled medication treatment (OR: 3.28, 95% CI: 2.29-4.70) were positively associated with vaccination. Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated (OR: 0.65, 95% CI: 0.45-0.96). Compared with unvaccinated participants, vaccinated participants adhered better to pharmacological and non-pharmacological treatment. CONCLUSIONS: Influenza and pneumococcal vaccination coverage are extremely low. Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.

Mortality and readmission risk for hospitalised patients with acute exacerbation of COPD with and without spirometric obstruction: a longitudinal observational study in China.

OBJECTIVE: To compare the clinical features and outcomes in patients with pre-chronic obstructive pulmonary disease (COPD) and COPD hospitalised for confirmed or suspected acute exacerbation of COPD (AECOPD). DESIGN: A multicentre, longitudinal observational cohort study. SETTING: Data were obtained from the AECOPD Inpatient Registry Study in China. PARTICIPANTS: 5896 patients hospitalised for AECOPD between 2017 and 2021. OUTCOMES: Patients were divided into the COPD (n=5201) and pre-COPD (n=695) groups according to the lung function test results. The outcomes of interest included all-cause, respiratory disease-related and cardiovascular disease-related deaths as well as readmissions within 30 days and 12 months after discharge. Cumulative incidence functions were used to estimate the risk of cause-specific mortality and readmission. Multivariate hazard function models were used to determine the association between lung function and outcomes. RESULTS: There were significant between-group differences in the symptoms at admission and medication use during hospitalisation. However, there was no significant between-group difference in the 30-day all-cause mortality (0.00 vs 2.23/1000 person-month (pm), p=0.6110) and readmission (33.52 vs 30.64/1000 pm, p=0.7175). Likewise, the 30-day and 12-month cause-specific outcomes were not significantly different between groups (30-day readmission with acute exacerbation (AE): 26.07 vs 25.11/1000 pm; 12-month all-cause mortality: 0.20 vs 0.93/1000 pm; all-cause readmission: 11.49 vs 13.75/1000 pm; readmission with AE: 9.15 vs 11.64/1000 pm, p>0.05 for all comparisons). Cumulative incidence curves revealed no significant between-group differences in the 30-day and 12-month prognosis (p>0.05). Multivariate analysis revealed no significant association of lung function categories with 30-day and 12-month mortality or readmission (p>0.05 for all effect estimations). CONCLUSIONS: Patients with pre-COPD have mild symptoms and similar risks for mortality and readmission during follow-up as patients with COPD. Patients with pre-COPD should receive optimal therapies before the occurrence of irreversible damage.

Multifunctional O-phenanthroline silver(I) complexes for antitumor activity against colorectal adenocarcinoma cells and antimicrobial properties by multiple mechanisms.

A series of O-phenanthroline silver(I) complexes were synthesized and characterized by infrared (IR) spectroscopy, mass spectrometry (MS), 1H nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray crystallography. The cytotoxicity of the silver(I) complex (P-131) was evaluated in the cancer cell lines HCT-116, HeLa, and MDA-MB-231 and the normal cell line LO2 via MTT assays. The 50% inhibition concentration (IC50) of P-131 on HCT116 cell line is 0.86 ± 0.03 µM. It is far lower than the IC50 value of cisplatin (9.08 ± 1.10 µM), the IC50 value of normal cell LO2 (76.20 ± 0.48 µM) is much higher than that of cisplatin (3.99 ± 0.74 µM), indicating that its anticancer effect is stronger than that of cisplatin, and its biological safety is greater than that of cisplatin. Furthermore, anticancer mechanistic studies showed that P-131 inhibited cell proliferation by blocking DNA synthesis and acted temporally on the nucleus in dividing HCT-116 cells. Moreover, P-131 increased intracellular reactive oxygen species (ROS) levels in a dose-dependent manner. Notably, 10 mg/kg P-131 showed better antitumor effects than oxaliplatin in an HCT116 human colorectal xenograft mouse model without inducing toxicity. Moreover, the microdilution broth method was used to evaluate the antimicrobial properties of P-131 against Pseudomonas aeruginosa and Candida albicans. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy.

Bleeding the Excited State Energy to the Utmost: Single-Molecule Iridium Complexes for In Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low-Power Laser.

A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrate high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato-/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808 nm laser irradiation by dual photodynamic therapy and photothermal therapy and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors.

Better response to Tanreqing injection in frequent acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients-Real-world evidence from a nationwide registry (ACURE) study.

Objective: Our aim was to systematically investigate the efficacy of Tanreqing (TRQ) injection on in-hospital outcomes among inpatients with frequent or infrequent AECOPD. Methods: In this ongoing, nationwide multicenter registry designed to investigate clinical characteristics, management, and prognoses of Chinese patients admitted for AECOPD in real-world settings, we collected characteristics, comorbidities, in-hospital prognoses, and information on the COPD assessment test (CAT) questionnaire, PEACE questionnaire, and modified British Medical Research Council (mMRC) questionnaire from each enrolled patient. Frequent AECOPD was determined as being admitted to the hospital ≥1 time or visiting the emergency room (ER) ≥ 2 times due to AECOPD within a year. A propensity match method and univariable and multivariable regression models were performed to analyze the efficacy of TRQ on clinical outcomes for inpatients with frequent AECOPD. Results: A total of 4135 inpatients were involved in the analysis, including 868 administered with TRQ and 3267 not administered with TRQ. After propensity score match, among those administered with TRQ, 493 had frequent AECOPD and 358 had infrequent AECOPD. A significant reduction of CAT score at discharge (TRQ median 12, IQR 8.0-16.0; non-TRQ median 13, IQR 9.0-18.0, p = 0.0297), a lower rate of ICU admission (TRQ 0.8% vs. non-TRQ 2.6%, p = 0.0191), and a shorter length of stay (LOS) (TRQ median 11, IQR 9.0-14.0; non-TRQ median 11, IQR 8.0-14.0, p = 0.004) were observed in the TRQ group, compared with the non-TRQ group among frequent AECOPD patients. In the subgroup analysis, for those with a PEACE score >7 on admission, TRQ contributed to a significantly lower CAT score at discharge (p = 0.0084) and a numerically lower ICU admission rate with a marginal statistical significance. Among those with phlegm-heat symptom complex on admission ≥2, a lower CAT score at discharge and a lower ICU admission were also observed in the TRQ group. Conclusion: TRQ injection had better efficacy in patients with frequent AECOPD in reducing ICU admission and alleviating respiratory symptoms, especially for those with higher severity on admission or more phlegm-heat symptoms.

The national COPD screening programme in China: rationale and design.

Background: COPD is the most prevalent chronic respiratory disease in China. It is estimated that there is a large, as-yet undetected, high-risk population who will develop in COPD in future. Methods and design: In this context, a nationwide COPD screening programme was launched on 9 October 2021. This multistage sequential screening programme incorporates a previously validated questionnaire (i.e. COPD Screening Questionnaire) and pre- and post-bronchodilator spirometry to target the COPD high-risk population. The programme plans to recruit 800 000 participants (eligible age 35-75 years) from 160 districts or counties of 31 provinces, autonomous regions or municipalities across China. The filtered COPD high-risk population and early-detected COPD patients will receive integrated management and be followed-up for ≥1 year. Discussion: This is the first large-scale prospective study to determine the net benefit of mass screening for COPD in China. Whether the smoking cessation rate, morbidity, mortality and health status of individuals at high risk of COPD could be improved along with this systematic screening programme will be observed and validated. Moreover, the diagnostic accuracy, cost-effectiveness and superiority of the screening programme will also be assessed and discussed. The programme marks a remarkable achievement in the management of chronic respiratory disease in China.

Dynamic analysis of gene signatures in the progression of COPD.

Aims: Oxidative stress is an important amplifying mechanism in COPD; however, it is unclear how oxidative stress changes and what its exact amplification mechanism is in the pathological process. We aimed to dynamically analyse the progression of COPD and further elucidate the characteristics of each developmental stage and unveil the underlying mechanisms. Methods: We performed a holistic analysis by integrating Gene Expression Omnibus microarray datasets related to smoking, emphysema and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification based on the concept of gene, environment and time (GET). Gene ontology (GO), protein-protein interaction (PPI) networks and gene set enrichment analysis (GSEA) were used to explore the changing characteristics and potential mechanisms. Lentivirus was used to promote HIF3A overexpression. Results: In smokers versus nonsmokers, the GO term mainly enriched in "negative regulation of apoptotic process". In later transitions between stages, the main enriched terms were continuous progression of "oxidation-reduction process" and "cellular response to hydrogen peroxide". Logistic regression showed that these core differentially expressed genes (DEGs) had diagnostic accuracy in test (area under the curve (AUC)=0.828) and validation (AUC=0.750) sets. GSEA and PPI networks showed that one of the core DEGs, HIF3A, strongly interacted with the ubiquitin-mediated proteolysis pathway. Overexpression of HIF3A restored superoxide dismutase levels and alleviated the reactive oxygen species accumulation caused by cigarette smoke extract treatment. Conclusion: Oxidative stress was continuously intensified from mild emphysema to GOLD 4; thus, special attention should be paid to the identification of emphysema. Furthermore, the downregulated HIF3A may play an important role in the intensified oxidative stress in COPD.

Pulmonary rehabilitation restores limb muscle mitochondria and improves the intramuscular metabolic profile.

BACKGROUND: Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated. METHODS: Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n  = 8), non-COPD/exercise ( n  = 7), COPD/rest ( n  = 7), COPD/medium exercise ( n  = 10), and COPD/intensive exercise ( n  = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). RESULTS: At the end of 90 days, COPD rats' weight gain was smaller than control by 59.48 ±â€Š15.33 g ( P  = 0.0005). The oxidative muscle fibers proportion was lower ( P  < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P  = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P  = 0.0093), myofibrils diameter (Δ0.06 µm, 95% CI: 0.02-0.10 µm, P  = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P  = 0.0434), mitochondria oxidative phosphorylate capacity ( P  < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. CONCLUSION: COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.