Search

Abstract Purpose This study aimed to preliminarily investigate the association and possible mechanisms between Helicobacter. pylori (H. pylori) infection and type 2 diabetes mellitus (T2DM) through data collection, statistical analysis, and bioinformatics analysis. Methods A retrospective cohort study, including a total of 4406 participants who attended annual health checkups at Xian GEM Flower Changqing Hospital, was conducted to explore the correlation between the incidence of T2DM and H. pylori infection. To uncover the potential mechanisms underlying the interaction between the two diseases, differentially expressed genes (DEGs) common to T2DM and H. pylori infection were identified using the GEO database and Venn diagrams. These DEGs were then analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) analysis. Results In total, 2053 participants were classified into the H. pylori-positive group and 2353 into the H. pylori-negative group. H. pylori infection was associated with a higher risk of T2DM occurrence (adjusted HR 1.59; 95% CI 1.17–2.15, P = 0.003). The average disease-free survival time was 34.81 months (95% CI 34.60-35.03 months) in the H. pylori positive group and 35.42 months (95% CI 35.28–35.56 months) in the H. pylori negative group. Multivariate analysis and subgroup analyses also showed that H. pylori infection increased the risk of developing T2DM. A total of 21 DEGs between T2DM and H. pylori infection were identified and enriched in 7 signaling pathways, indicating specific protein interactions. Conclusions The prevalence of T2DM was associated with H. pylori infection. T2DM and H. pylori infection may interact with each other through metabolic and immune pathways.

Abstract. 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.

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.

ObjectivesTo explore the impact of diabetes itself and glycemic control status on tuberculosis (TB).MethodsA 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.ResultsIn 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

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.

BackgroundPrevious 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.ObjectivesThe purpose of this retrospective cohort study was to investigate the impact of immune breakthroughs on disease progression and prognosis in patients with COVID-19.MethodsA 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.ResultsThe 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

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.

Abstract. 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 ± 15.33 g (P = 0.0005). The oxidative muscle fibers proportion was lower (P

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.

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.

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.

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.

Abstract Background Coronary artery disease (CAD) is a common comorbidity of chronic obstructive pulmonary disease (COPD). However, data related to the impact of CAD on outcomes of acute exacerbation of COPD (AECOPD) are limited and whether the relationship depends on sex remains unknown. Our aim was to determine the impact of comorbid CAD on clinical outcomes among men and women with AECOPD. Methods We used data from the acute exacerbation of chronic obstructive pulmonary disease inpatient registry (ACURE) study, which is a nationwide observational real-world study conducted between September 2017 and February 2020 at 163 centers in patients admitted with AECOPD as their primary diagnosis. Patients were stratified according to the presence or absence of CAD in men and women. The primary outcomes were the length of hospital stay and economic burden during hospitalization. Results Among 3906 patients included in our study, the prevalence of CAD was 17.0%, and it was higher in women than in men (19.5% vs. 16.3%; P = 0.034). Age and other cardiovascular diseases were common factors associated with comorbid CAD in men and women, while body-mass index, cerebrovascular disease, and diabetes were determinants in men and pre-admission use of long-acting beta-adrenoceptor agonist and home oxygen therapy were protective factors in women. Only in men, patients with CAD had a longer length of hospital stay (median 10.0 vs. 9.0 days, P

ObjectivePulmonary hypertension (PH) in context with interstitial lung disease (ILD) portends serious clinical consequences and a high rate of mortality. Recently published randomized controlled trials (RCTs) which assessed the pulmonary arterial hypertension (PAH)-specific drugs for pulmonary hypertension and interstitial lung disease (PH-ILD) revealed inconsistent clinical outcomes with previous studies. We conducted a systemic review and meta-analysis to further investigate the effect of PAH-specific therapies for PH-ILD.MethodsClinical trials were searched from the EMBASE, PUBMED, and CENTRAL databases. The duration from the establishment of the database to June 2022 for RCTs evaluates the effect of PAH-specific therapy in patients with PH-ILD. RevMan 5.4 was used for the meta-analysis.ResultsA total of six articles (with a total of 791 patients) were included, including 412 patients in the treated group and 379 patients in the control group. As compared to placebo, the change of 6MWD was a significant improvement with PAH-specific therapy in the six RCTs (23.09; 95% CI, 12.07–34.12 P < 0.0001); but when the study with inhaled treprostinil was excluded, the significant improvement in the change of 6MWD from baseline was not present anymore (MD 11.01, 95%CI−6.43–28.46 P = 0.22). There was no significant improvement in the change in lung function, hemodynamic parameters, clinical worsening, all-cause death, and serious adverse effects in the treated group compared to placebo.ConclusionPAH-specific therapy significantly improved exercise capacity in the patients with PH-ILD, but this is due to the greater contribution of the study with inhaled treprostinil. Therefore, our findings still did not support the routine use of the whole PAH-specific drugs for PH-ILD.

Objective The clinical importance of aberrantly expressed microRNAs (miRNAs) in diagnosing inflammatory bowel disease (IBD) has not been well established, so was investigated in this systematic review and meta-analysis. Methods Articles in online databases from inception to March 17, 2021 were retrieved. Random effects meta-analysis was used to obtain sensitivity, specificity, positive (PLRs) and negative likelihood ratios (NLRs), diagnostic odds ratios (DORs), and areas under the curve (AUC) with 95% confidence intervals (CI) for IBD diagnosis. Results Of 117 studies reporting altered miRNA expression in IBD included in the systematic review, 15 involving 937 patients with IBD and 707 controls, 22 miRNAs, and two miRNA panels were eligible for meta-analysis. Pooled analyses showed a moderate diagnostic accuracy for miRNAs in the IBD diagnosis, with a sensitivity of 0.80 (95% CI: 0.79–0.82), specificity of 0.84 (95% CI: 0.82–0.86), DOR of 21.19 (95% CI: 13.90–32.31), and AUC of 0.89. Subgroup analyses revealed a better performance in patients with ulcerative colitis (AUC, 0.93) than Crohn’s disease (AUC, 0.84). Consistent upregulation of miR-21, miR-16, and miR-192 in blood with a high-moderate diagnostic accuracy was found in at least two studies. Conclusions These findings suggest miRNAs are credible diagnostic biomarkers in IBD.

Background Non‐small cell lung cancer (NSCLC) is a leading subtype in lung cancer, with high morbidities and mortalities worldwide. microRNA (miRNA) has appeared to play indispensable roles in a variety of solid carcinomas. The current study focused on the functions of miR‐100 in NSCLC. Methods qRT‐PCR was performed to detect miR‐100 and HOXA1 expressions in NSCLC tissues and cells. MTT and transwell assays were used to determine the functions of miR‐100 in NSCLC cell proliferation, invasion and migration abilities. Western blot was used to measure related protein expressions. Results qRT‐PCR results showed that miR‐100 expressions were dramatically decreased in NSCLC tissues. MTT assays indicated that miR‐100 restoration inhibited NSCLC cell proliferation. Furthermore, transwell assay was performed to determine the impacts of miR‐100 on NSCLC invasion and migration abilities. As expected, the invasion and migration capacities were significantly repressed. Direct interactions between HOXA1 and miR‐100 were also verified via dual‐luciferase reporter assays. Western blot analysis demonstrated that miR‐100 exerted suppressive functions via regulating EMT and Wnt/β‐catenin in NSCLC cells. Conclusions Our results showed that miR‐100 served antitumor roles in NSCLC, providing new evidence of miR‐100 as a promising therapeutic biomarker in NSCLC.

Background: Although medical guidelines discourage the use of methylxanthines in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), they are still widely used in clinical practice. This study investigated the real-world use of methylxanthines in the management of AECOPD.Methods: Patient data from the Acute exacerbation of Chronic obstructive pulmonary disease Using REgistry data (ACURE, NCT02657525) study database were screened. Enrolled patients were divided into treatment and control groups. Propensity score (PS) matching and Cox regression analyses were used to minimize confounding factors and determine the association between methylxanthine treatment and the length of stay (LOS).Results: Among the 2088 eligible patients, 1,563 (74.9%) were in the methylxanthine treatment group. Patients treated with methylxanthines had more severe respiratory symptoms and worse lung function than those in the control group. Doxophylline was the most commonly used methylxanthine in both secondary and tertiary hospitals. After PS matching, 966 patients were equally divided into two groups. The LOS of patients in the two groups was similar [median: 8 days, interquartile range (IQR): 7–11 days, p = 0.730]. Patients in the treatment group (median: 8, IQR: 4–12) had a more significant decrease in the COPD Assessment Test score from admission to discharge than those in the control group (median: 6, IQR: 2–10, p < 0.001). Among all matched patients, the LOS was not significantly associated with methylxanthine treatment [adjusted hazard ratio (HR): 1.02, 95% confidence intervals (CIs): 0.89–1.16]. However, in the subgroup analysis, methylxanthines were significantly associated with a short LOS in patients with blood eosinophil count >4% (adjusted HR: 1.56, 95% CIs: 1.12–2.17).Conclusion: This study revealed that methylxanthines, especially doxophylline, are widely used in China. Methylxanthines were effective in improving symptoms in AECOPD patients. Higher blood eosinophil count may be associated with a better efficacy of methylxanthine treatment.

Accurate measurement of relative permeability curve is the basis for evaluating gas reservoir performance. The unsteady-state method could bring significant measurement error for low-permeability cores. However, it is difficult to control the constant gas flow rate in the traditional steady-state method, which obstacles the experimental operation. In this study, an improved steady-state method was proposed. First, the pressure value obtained from the experiment, when the gas permeability no longer changed with the average pressure on the rock core, was set as the testing pressure. Then, the gas was injected under constant pressure, and the water was injected with a constant flow rate. Finally, the relative permeability values of gas and water phases were calculated based on Darcy’s law. Comparative analysis of the results of the relative permeability curves under formation pressure and pressure with negligible slip effect indicates that the relative permeability curves are the same in gas and water phases, proving the feasibility of the new method. Further, the results were compared with those of the test method at normal pressure, the water-phase relative permeability showed no significant change, the relative permeability of gas phase was larger, the two-phase flow area became wider, and the irreducible water saturation was lower than that at the normal pressure. This result reflects that pressure does not significantly affect the flow of wetting phase but tremendously influences the nonwetted phase under low pressure. The relationship between relative permeability and water saturation is linear in the semilogarithmic coordinate diagram and can be described by using the following relationship: ln krg/krw=aSw+ln b. With the decrease in the core permeability, relative permeability curve, and isotonic point moved to the right, irreducible water saturation gradually increased, and residual gas saturation decreased, indicating that the smaller permeability induced a lower gas-phase flow capacity.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic inflammation, emphysema, airway remodeling, and altered lung function. Despite the canonical classification of COPD as a neutrophilic disease, blood and airway eosinophilia are found in COPD patients. Identifying the tools to assess eosinophilic airway inflammation in COPD models during stable disease and exacerbations will enable the development of novel anti-eosinophilic treatments. We developed different animal models to mimic the pathological features of COPD. Our results show that eosinophils accumulated in the lungs of pancreatic porcine elastase-treated mice, with emphysema arising from the alveolar septa. A lipopolysaccharide challenge significantly increased IL-17 levels and induced a swift change from a type-2 response to an IL-17-driven inflammatory response. However, lipopolysaccharides can exacerbate cigarette smoking-induced airway inflammation dominated by neutrophil infiltration and airway remodeling in COPD models. Our results suggest that eosinophils may be associated with emphysema arising from the alveolar septa, which may be different from the small airway disease-associated emphysema that is dominated by neutrophilic inflammation in cigarette smoke-induced models. The characterization of heterogeneity seen in the COPD-associated inflammatory signature could pave the way for personalized medicine to identify new and effective therapeutic approaches for COPD.

Background: Lipid-lowering therapy is very important in secondary prevention of coronary heart disease (CHD). In many clinical trials, it has been found that Sodium Tanshinone IIA Sulfonate Injection (STS) have a lipid-lowering effect while reducing major cardiovascular events in patients with CHD. However, up to now, there is no system review on the effectiveness and safety of STS affecting blood lipids.Purpose: The aim of this review is to systematically assess the effects of STS on blood lipid levels in patients with CHD.Methods: Until Mar 2021, five databases (PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database) were searched for randomized controlled trials (RCTs) about STS treating patients with CHD. Risk bias was assessed for included studies according to Cochrane handbook. The primary outcome was total cholesterol (TC). The secondary outcomes were triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and adverse events (AEs).Results: A total of 27 trials including 2,445 CHD patients met the eligibility criteria. Most trials had high risks in random sequence generation, allocation concealment, blinding of patients and personal, blinding of outcome assessment. Meta-analysis showed that STS significantly reduced plasma TC levels [MD = −1.34 mmol/l 95% CI (−1.59, −1.09), p < 0.00001, I2 = 98%], TG levels [MD = −0.49 mmol/l 95% CI (−0.62, −0.35), p < 0.00001, I2 = 97%], LDL-c levels [MD = −0.68 mmol/l (−0.80, −0.57), p < 0.00001, I2 = 96%], increased HDL-c levels [MD = 0.26 mmol/l (0.15, 0.37), p < 0.00001, I2 = 97%], without increasing the incidence of AEs [RR = 1.27 95% CI (0.72, 2.27), p = 0.94, I2 = 0%] in patients with CHD.Conclusion: STS can safely and effectively reduce plasma TC, TG and LDL-c levels in patients with CHD, and improve plasma HDL-c levels. However, these findings require careful recommendation due to the low overall quality of RCTs at present. More multi-center, randomized, double-blind, placebo-controlled trials which are designed follow the CONSORT 2010 guideline are needed.

Background: Cardiac rehabilitation is an important part of the therapeutic regimen for chronic heart failure. Acute decompensated heart failure (ADHF) in hospitalized patients were usually excluded from cardiac rehabilitation programs. The initiation of cardiac rehabilitation with ADHF usually occurs after hospital discharge. This study included recent clinical trials in patients beginning early exercise-based rehabilitation during their hospitalization and compared the efficacy and safety of early cardiac rehabilitation to ADHF patients who didn’t receive cardiac rehabilitation. Methods: Clinical trials were searched from the EMBASE, PubMed, CENTRAL, and WAN FANG. We included randomized controlled trials (RCTs) in which early exercise-based rehabilitation started during the index hospitalization, from the establishment of the database to July 2022. RevMan 5.4 was used for the statistical analysis. Results: Six studies, with a total of 668 patients were included; 336 patients in the early rehabilitation group and 332 patients in the control group. Exercise capacity was significantly improved in the 6-minute walk distance [mean difference (MD): 32.97, 95% CI: 31.03 to 34.90, p < 0.00001], and the Short Physical Performance Battery (MD: 1.40, 95% CI: 1.35 to 1.44, p < 0.00001). The rate of all-cause rehospitalization was significantly decreased in the early rehabilitation group (OR: 0.67, 95% CI: 0.45 to 0.99, p = 0.04). Conclusions: Early exercise-based rehabilitation for eligible ADHF in-patients starting during, or early after, hospitalization could significantly improve exercise capacity. A transitional, individualized, progressive, exercise-based rehabilitation program during hospitalization combined with post-discharge clinic rehabilitation is an integrated rehabilitation strategy for acute decompensated heart failure.

Abundant oil and gas reserves have been proved in carbonates, but formation damage affects their production. In this study, the characteristics and formation-damage mechanism of the carbonate reservoir formation of the MS Oilfield in the Middle East were analyzed—utilizing X-ray diffraction, a scanning electron microscope, slice identification, and mercury intrusion—and technical measures for preventing formation damage were proposed. An ‘improved ideal filling for temporary plugging’ theory was introduced, to design the particle size distribution of acid-soluble temporary plugging agents; a water-based drill-in fluid, which did not require gel-breaker treatment, was formed, and the properties of the drill-in fluid were tested. The results showed that the overall porosity and permeability of the carbonate reservoir formation were low, and that there was a potential for water-blocking damage. There were micro-fractures with a width of 80–120 μm in the formation, which provided channels for drill-in fluid invasion. The average content of dolomite is 90.25%, and precipitation may occur under alkaline conditions. The polymeric drill-in fluid had good rheological and filtration properties, and the removal rate of the filter cake reached 78.1% in the chelating acid completion fluid without using gel breakers. In the permeability plugging test, the drill-in fluid formed a tight plugging zone on the surface of the ceramic disc with a pore size up to 120 μm, and mitigated the fluid loss. In core flow tests, the drill-in fluid also effectively plugged the formation core samples by forming a thin plugging layer, which could be removed by the chelating acid completion fluid, indicated by return permeability higher than 80%. The results indicated that the drill-in fluid could mitigate formation damage without the treatment of gel breakers, thus improving the operating efficiency and safety.

Background and Objective: Elevated eosinophils in chronic obstructive pulmonary disease (COPD) are recognized as a biomarker to guide inhaled corticosteroids use, but the value of blood eosinophils in hospitalized exacerbations of COPD remains controversial. This study aimed to evaluate the accuracy of eosinophils in predicting clinical outcomes in acute exacerbation of COPD (AECOPD).Methods: We analyzed data from the acute exacerbation of chronic obstructive pulmonary disease inpatient registry (ACURE) study, which is an ongoing nationwide multicenter, observational real-world study in patients admitted for AECOPD. Data collected between January 2018 and December 2019 in 163 centers were first reviewed. The eligible patients were divided into eosinophilic and non-eosinophilic groups, according to blood eosinophil with 2% of the total leukocyte count as the threshold. Propensity score (PS) matching was performed to adjust for confounders.Results: A total of 1,566 patients (median age: 69 years; 80.3% male) were included and 42.7% had an eosinophilic AECOPD. Eosinophil count

Abstract To study the influence of pore structure on the seepage and water‐drive producing mechanisms, various methods were combined to describe the micro‐pore structure in the Chang 6 tight sandstone reservoir in the Huaqing area, Ordos Basin, China. Nuclear magnetic resonance (NMR) was combined with displacement experiments to determine the distribution of oil and water in pores of different scales before and after water flooding. There are few micro pores in the reservoir. As permeability increases, the distribution of nano pores decreases, while sub‐micro pores increase. Also, sub‐micro pores are the main pathway within the reservoir. There is a negative power function correlation between the minimum starting pressure gradient of the oil (Swc) and maximum throat radius. Also, with a decrease of permeability, smaller pore throats become more abundant and the nonlinear section of the flow velocity‐differential pressure curves increase. There is a large amount of crude oil gathering in the nano pores. As permeability increases, the main sources of movable oil are from the nano pores (kg 1.0 × 10−3 μm2). Displacement efficiency is always the highest in sub‐micro pores.

Background: In patients with chronic obstructive pulmonary disease (COPD), acute exacerbations affect patients' health and can lead to death. This study was aimed to develop a prediction model for in-hospital mortality in patients with acute exacerbations of COPD (AECOPD).Method: A retrospective study was performed in patients hospitalized for AECOPD between 2015 and 2019. Patients admitted between 2015 and 2017 were included to develop model and individuals admitted in the following 2 years were included for external validation. We analyzed variables that were readily available in clinical practice. Given that death was a rare outcome in this study, we fitted Firth penalized logistic regression. C statistic and calibration plot quantified the model performance. Optimism-corrected C statistic and slope were estimated by bootstrapping. Accordingly, the prediction model was adjusted and then transformed into risk score.Result: Between 2015 and 2017, 1,096 eligible patients were analyzed, with a mean age of 73 years and 67.8% male. The in-hospital mortality was 2.6%. Compared to survivors, non-survivors were older, more admitted from emergency, more frequently concomitant with respiratory failure, pneumothorax, hypoxic-hypercarbic encephalopathy, and had longer length of stay (LOS). Four variables were included into the final model: age, respiratory failure, pneumothorax, and LOS. In internal validation, C statistic was 0.9147, and the calibration slope was 1.0254. Their optimism-corrected values were 0.90887 and 0.9282, respectively, indicating satisfactory discrimination and calibration. When externally validated in 700 AECOPD patients during 2018 and 2019, the model demonstrated good discrimination with a C statistic of 0.8176. Calibration plot illustrated a varying discordance between predicted and observed mortality. It demonstrated good calibration in low-risk patients with predicted mortality rate ≤10% (P = 0.3253) but overestimated mortality in patients with predicted rate >10% (P < 0.0001). The risk score of 20 was regarded as a threshold with an optimal Youden index of 0.7154.Conclusion: A simple prediction model for AECOPD in-hospital mortality has been developed and externally validated. Based on available data in clinical setting, the model could serve as an easily used instrument for clinical decision-making. Complications emerged as strong predictors, underscoring an important role of disease management in improving patients' prognoses during exacerbation episodes.

Objectives To identify factors associated with length of stay (LOS) in chronic obstructive pulmonary disease (COPD) hospitalised patients, which may help shorten LOS and reduce economic burden accrued over hospital stay.Design A retrospective cohort study.Setting This study was performed in a tertiary hospital in China.Participants Patients with COPD who were aged ≥40 years and newly admitted between 2016 and 2017.Primary and secondary outcome measures LOS at initial admission was the primary outcome and health expenditures were the secondary outcome. To identify factors associated with LOS, we collected information at index hospitalisation and constructed a conceptual model using directed acyclic graph. Potential factors were classified into five groups: demographic information, disease severity, comorbidities, hospital admission and environmental factors. Negative binomial regression model was fitted for each block of factors and a parsimonious analysis was performed.Results In total, we analysed 565 patients with COPD. The mean age was 69±11 years old and 69.4% were men. The median LOS was 10 (interquartile range 8–14) days. LOS was significantly longer in patients with venous thromboembolism (VTE) (16 vs 10 days, p=0.0002) or with osteoporosis (15 vs 10 days, p=0.0228). VTE ((rate ratio) RR 1.38, 95% CI 1.07 to 1.76), hypoxic–hypercarbic encephalopathy (RR 1.53, 95% CI 1.06 to 2.20), respiratory infection (RR 1.12, 95% CI 1.01 to 1.24), osteoporosis (RR 1.45, 95% CI 1.07 to 1.96) and emergence admission (RR 1.08, 95% CI 1.01 to 1.16) were associated with longer LOS. In parsimonious analysis, all these factors remained significant except emergency admission, highlighting the important role of concomitant morbidities in patients’ hospital stay. Total hospitalisation cost and patients’ out-of-pocket cost increased monotonically with LOS (both ptrend

Low-permeability reservoirs have tiny pores with winding and complicated pore throats. The oil recovery efficiency of low-permeability reservoirs can be enhanced through the displacement of reservoir oil through imbibition. In the present study, experiments were conducted to investigate variations in the imbibition height of hydrophilic and weakly-hydrophilic rock samples under different interfacial tensions. An imbibition model considering imbibition resistance and bending of pore throats was established based on fractal theory. According to the experimental results, variations in the imbibition height of low-permeability rock samples with time can be divided into three stages. In the first stage, the capillary force plays a dominant role, while the viscous force and gravity have very slight effects. The imbibition height first increases rapidly and then levels off to a constant rate. With the increase in interfacial tension, the imbibition rate in the first stage increases, the ultimate imbibition height increases initially and then decreases, and the contribution of the imbibition height in the first stage to the ultimate imbibition height becomes greater. There is an optimal interfacial tension that causes the ultimate imbibition height to reach its maximum. The calculated results obtained from the proposed imbibition model are consistent with the experimental results, indicating that the model can accurately reflect the change in the imbibition height in low-permeability reservoirs in the first stage.

To explore variations in the transcription activity during spermiogenesis, round and elongated spermatids were collected from ICR/CD1 model mice using laser capture microdissection (LCM) and cauda epididymal sperm samples. The transcripts were sequenced using RNA-seq, and the reads were mapped to mm9. The majority of the reads (70%) in the round and elongated spermatids were mappable to known and predicted exons, but that in sperm was only 9%. The results of the distribution of reads suggested that alternative splicing was more complicated in sperm than in round and elongated spermatids. In the 19,127 genes, we detected the expression of 5,104 de novo genes and 91,112 alternative splicing events, and 12,105 were differentially expressed. Gene ontology (GO), InterPro domains, and KEGG revealed changes in gene transcription, mitochondrial protein translation, cellular components, and energy metabolism during spermiogenesis. The results provided considerable information about alternative splicing events, differentiallly expressed genes (DEGs), and novel transcriptions during spermiogenesis in mice.

Mosquito densoviruses (DNVs) are candidate agents for paratransgenic control of malaria and other vector-borne diseases. Unlike other mosquito DNVs, the Anopheles gambiae DNV (AgDNV) is non-pathogenic to larval mosquitoes. However, the cost of infection upon adults and the molecular mechanisms underpinning infection in the mosquito host are unknown. Using life table analysis, we show that AgDNV infection has minimal effects on An. gambiae survival (no significant effect in 2 replicates and a slight 2 day survival decrease in the third replicate). Using microarrays, we show that AgDNV has very minimal effect on the adult mosquito transcriptome, with only 4–15 genes differentially regulated depending on the statistical criteria imposed. The minimal impact upon global transcription provides some mechanistic understanding of lack of virus pathogenicity, suggesting a long co-evolutionary history that has shifted towards avirulence. From an applied standpoint, lack of strong induced fitness costs makes AgDNV an attractive agent for paratransgenic malaria control.

The endosymbiotic bacterium Wolbachia is being investigated as a potential control agent in several important vector insect species. Recent studies have shown that Wolbachia can protect the insect host against a wide variety of pathogens, resulting in reduced transmission of parasites and viruses. It has been proposed that compromised vector competence of Wolbachia-infected insects is due to up-regulation of the host innate immune system or metabolic competition. Anopheles mosquitoes, which transmit human malaria parasites, have never been found to harbor Wolbachia in nature. While transient somatic infections can be established in Anopheles, no stable artificially-transinfected Anopheles line has been developed despite numerous attempts. However, cultured Anopheles cells can be stably infected with multiple Wolbachia strains such as wAlbB from Aedes albopictus, wRi from Drosophila simulans and wMelPop from Drosophila melanogaster. Infected cell lines provide an amenable system to investigate Wolbachia-Anopheles interactions in the absence of an infected mosquito strain. We used Affymetrix GeneChip microarrays to investigate the effect of wAlbB and wRi infection on the transcriptome of cultured Anopheles Sua5B cells, and for a subset of genes used quantitative PCR to validate results in somatically-infected Anopheles mosquitoes. Wolbachia infection had a dramatic strain-specific effect on gene expression in this cell line, with almost 700 genes in total regulated representing a diverse array of functional classes. Very strikingly, infection resulted in a significant down-regulation of many immune, stress and detoxification-related transcripts. This is in stark contrast to the induction of immune genes observed in other insect hosts. We also identified genes that may be potentially involved in Wolbachia-induced reproductive and pathogenic phenotypes. Somatically-infected mosquitoes had similar responses to cultured cells. The data show that Wolbachia has a profound and unique effect on Anopheles gene expression in cultured cells, and has important implications for mechanistic understanding of Wolbachia-induced phenotypes and potential novel strategies to control malaria.

Paratransgenesis, the genetic manipulation of insect symbiotic microorganisms, is being considered as a potential method to control vector-borne diseases such as malaria. The feasibility of paratransgenic malaria control has been hampered by the lack of candidate symbiotic microorganisms for the major vector Anopheles gambiae. In other systems, densonucleosis viruses (DNVs) are attractive agents for viral paratransgenesis because they infect important vector insects, can be genetically manipulated and are transmitted to subsequent generations. However, An. gambiae has been shown to be refractory to DNV dissemination. We discovered, cloned and characterized the first known DNV (AgDNV) capable of infection and dissemination in An. gambiae. We developed a flexible AgDNV-based expression vector to express any gene of interest in An. gambiae using a two-plasmid helper-transducer system. To demonstrate proof-of-concept of the viral paratransgenesis strategy, we used this system to transduce expression of an exogenous gene (enhanced green fluorescent protein; EGFP) in An. gambiae mosquitoes. Wild-type and EGFP-transducing AgDNV virions were highly infectious to An. gambiae larvae, disseminated to and expressed EGFP in epidemiologically relevant adult tissues such as midgut, fat body and ovaries and were transmitted to subsequent mosquito generations. These proof-of-principle data suggest that AgDNV could be used as part of a paratransgenic malaria control strategy by transduction of anti-Plasmodium peptides or insect-specific toxins in Anopheles mosquitoes. AgDNV will also be extremely valuable as an effective and easy-to-use laboratory tool for transient gene expression or RNAi in An. gambiae.