Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 µg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in the annual decline in the FEV1 before and after bronchodilator use from day 30 to month 24. RESULTS: Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (±SE) annual decline in the FEV1 before bronchodilator use: the decline was 38±6 ml per year in the tiotropium group and 53±6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P=0.06). In contrast, the annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P=0.006). The incidence of adverse events was generally similar in the two groups. CONCLUSIONS: Tiotropium resulted in a higher FEV1 than placebo at 24 months and ameliorated the annual decline in the FEV1 after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).

Development and validation of a genomic nomogram based on a ceRNA network for comprehensive analysis of obstructive sleep apnea.

Objectives: Some ceRNA associated with lncRNA have been considered as possible diagnostic and therapeutic biomarkers for obstructive sleep apnea (OSA). We intend to identify the potential hub genes for the development of OSA, which will provide a foundation for the study of the molecular mechanism underlying OSA and for the diagnosis and treatment of OSA. Methods: We collected plasma samples from OSA patients and healthy controls for the detection of ceRNA using a chip. Based on the differential expression of lncRNA, we identified the target genes of miRNA that bind to lncRNAs. We then constructed lncRNA-related ceRNA networks, performed functional enrichment analysis and protein-protein interaction analysis, and performed internal and external validation of the expression levels of stable hub genes. Then, we conducted LASSO regression analysis on the stable hub genes, selected relatively significant genes to construct a simple and easy-to-use nomogram, validated the nomogram, and constructed the core ceRNA sub-network of key genes. Results: We successfully identified 282 DElncRNAs and 380 DEmRNAs through differential analysis, and we constructed an OSA-related ceRNA network consisting of 292 miRNA-lncRNAs and 41 miRNA-mRNAs. Through PPI and hub gene selection, we obtained 7 additional robust hub genes, CCND2, WT1, E2F2, IRF1, BAZ2A, LAMC1, and DAB2. Using LASSO regression analysis, we created a nomogram with four predictors (CCND2, WT1, E2F2, and IRF1), and its area under the curve (AUC) is 1. Finally, we constructed a core ceRNA sub-network composed of 74 miRNA-lncRNA and 7 miRNA-mRNA nodes. Conclusion: Our study provides a new foundation for elucidating the molecular mechanism of lncRNA in OSA and for diagnosing and treating OSA.

The influence of sex on anthropometric methods and four scales for screening obstructive sleep apnea.

OBJECTIVES: Obstructive Sleep Apnea (OSA) is a kind of respiratory disease that occurs apnea repeatedly during sleep. The purpose of this study was to investigate the influence of sex on anthropometric methods and four scales for screening OSA. METHODS: The basic data and PSG data of 2108 patients who underwent PSG examination at the Sleep Medicine Center of the First Affiliated Hospital of Guangzhou Medical University from July 2017 to December 2020 were continuously included. Then the sensitivity, specificity, positive predictive value, negative predictive value, AUC and DOR of the anthropometric method and the four scales were calculated. RESULTS: 2108 OSA patients were enrolled from the Sleep Medicine Center, including 1644 males (78.0%). The average neck circumference and waist circumference of male and female patients were respectively (39.4±3.4) cm and (96.7±13.8) cm,(34.6±3.5) cm and (90.1±11.6) cm. In female patients. the AUC of NoSAS was the largest. When AHI was 5, 15, and 30 evens/h as the cut-off point, in male patients, the sensitivity of NHR was the highest,in female patients, the sensitivity of WHR was the highest. CONCLUSIONS: NHR and WHR are good tools for screening OSA in male and female patients respectively. They are worthy of promotion.

Safety and efficacy of a novel double-lumen tracheal tube in neonates with RDS: A prospective cohort study.

Background: The purpose of this study was to assess the safety and efficacy of a new double-lumen tracheal tube for neonates, with a conventional tracheal tube as a control. Method: Newborns with respiratory distress syndrome (RDS) requiring endotracheal intubation admitted to the tertiary neonatal intensive care unit (NICU) of Qujing Maternal and Child Healthcare Hospital in Yunnan Province between March 2021 and May 2022 were enrolled in this prospective cohort study. Outcome indicators related to effectiveness included mainly the number of intubations, duration of ventilation, duration of oxygenation, and length of stay; safety indicators included any clinical adverse effects during and after intubation. Appropriate stratified and subgroup analyses were performed according to the purpose of intubation, gestational age, and whether the drug was administered via endotracheal tube. Result: A total of 101 neonates were included and divided into two groups based on the choice of tracheal tube: the conventional (n = 50) and new (n = 51) tracheal tube groups. There was no statistical difference between the two groups in terms of adverse effects during and after intubation (p > 0.05). In neonates who were mechanically ventilated without endotracheal surfactant therapy or newborns receiving InSurE technique followed by non-invasive ventilation, no significant differences were found between the two groups regarding any of the efficacy indicators (p > 0.05). However, for neonates on invasive mechanical ventilation, the new tracheal tube allowed for a significant reduction in the duration of mechanical ventilation (96.50[74.00, 144.00] vs. 121.00[96.00, 196.50] hours, p = 0.037) and total ventilation (205.71 ± 80.24 vs. 277.56 ± 117.84 h, p = 0.027), when used as a route for endotracheal drug delivery. Further analysis was performed according to gestational age for newborns requiring intratracheal surfactant administration during mechanical ventilation, and the data showed that for preterm infants, the new tracheal tube not only shortened the duration of mechanical ventilation (101.75 ± 39.72 vs. 155.50 ± 51.49 h, p = 0.026) and total ventilation (216.00 ± 81.60 vs. 351.50 ± 113.79 h, p = 0.010), but also demonstrated significant advantages in reducing the duration of oxygen therapy (9.75 ± 6.02 vs. 17.33 ± 8.43 days, p = 0.042); however, there was no statistical difference in efficacy outcomes between the two groups in full-term infants (p > 0.05). Conclusion: The efficacy and safety of this new tracheal tube are promising in neonates with RDS, especially those requiring surfactant administration via a tracheal tube during mechanical ventilation. Given the limitations of this study, however, the clinical feasibility of this catheter needs to be further confirmed in prospective randomized trials with larger sample sizes. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=122073.

Comparison of six assessment tools to screen for obstructive sleep apnea in patients with hypertension.

BACKGROUND: Obstructive sleep apnea (OSA) is often accompanied by other complications, especially hypertension. HYPOTHESIS: The purpose of this study is to compare the application value of six tools in the screening of OSA in patients with hypertension. Compared with other questionnaires, we hypothesized that Berlin performed better in screening hypertensive patients suspected of OSA. METHODS: In this study, we collected the basic data and polysomnography (PSG) data of patients diagnosed with hypertension who underwent PSG at the Sleep Medicine Center of the First Affiliated Hospital of Guangzhou Medical University from April 2012 to March 2021. The sensitivity, specificity, positive predictive value, negative predictive value, area under the curv (AUC) and diagnostic odds ratio (DOR) of the six screening tools were then calculated, and their correlation with the sleep apnea hypopnea index (AHI) analyzed. RESULTS: There were 303 males (303/398, 76.1%) out of 398 hypertension patients suspected of OSA. The area under the curve of the Berlin questionnaire's receiver operating characteristic (ROC) curve reached 0.753 (95%CI: 0.707-0.794). When the AHI was 5, 15 and 30 times/h as the cut-off points, the sensitivity and negative predictive value of Berlin were the highest at 0.947 and 0.630, 0.970 and 0.851, and 0.988 and 0.957 respectively, while the specificity and positive predictive value of the Epworth Sleepiness Scale (ESS) were the highest at 0.696 and 0.729, 0.750 and 0.887, and 0.674 and 0.575 respectively. The DOR value of the Berlin questionnaire could reach 18.333 when the AHI cut-off point was 30 times/h. Berlin had the largest rank correlation coefficient with AHI at 0.466. CONCLUSION: The Berlin questionnaire can be considered a priority for the screening and stratifying of hypertensive patients suspected of OSA.

MiR-499-5p protects cardiomyocytes against ischaemic injury via anti-apoptosis by targeting PDCD4.

Recent studies have reported that miRNAs might play critical roles in acute myocardial infarction (AMI). The objective of this study is to investigate the role of miR-499-5p in AMI and its potential molecular mechanisms. The expression level of MiR-499-5p was remarkably decreased in the infarcted myocardial tissues and in the cultured neonatal rat cardiomyocytes induced by hypoxia. Overexpression or knockdown of miR-499-5p decreased or increased the apoptotic rates of cultured cardiomyocytes in vitro. In addition, ectopic overexpression of miR-499-5p in the rat AMI models with agomir reduced the myocardial infarct size through decreasing the cardiomyocytes apoptosis in the infarcted area of the rat hearts. PDCD4 (programmed cell death 4) was verified as a direct target of miR-499-5p by luciferase report assay, and ectopic overexpression or inhibition of miR-499-5p could inhibit or increase the PDCD4 expression at both the mRNA and protein levels. Furthermore, we found that ectopic overexpression of PDCD4 without miR-499-5p binding sites reversed miR-499-5p-mediated cardiomyocytes apoptosis. Together, these findings revealed the role of miR-499-5p in protecting the cardiomyocytes against apoptosis induced by AMI via its direct target PDCD4, which providing evidence for the miR-499-5p/PDCD4 pathway as a potential therapeutic target for patients with AMI.

[Current situation and effect of non-hazardous treatment of excrement of sanitary latrines in rural schistosomiasis endemic areas of Eryuan County, Yunnan Province].

OBJECTIVE: To understand the condition of the construction and management of sanitary latrines, and assess the effect of disposal of the excrement in rural schistosomiasis endemic areas in Yunnan Province. METHODS: Three villages with schistosomiasis endemic were selected from Eryuan County and 30 households per village were sampled randomly for the field survey. The stool samples were sampled and tested according to the national standard. RESULTS: Totally 90 latrines were surveyed. The popularity rates of sanitary latrines in Yongle, Qiandian and Xinzhuang villages were 83.19%, 83.12% and 81.63% respectively. In the 90 household latrines, only 32.22% located inside the courtyard, and 91.67% of sanitary latrines and 70.00% of non-sanitary latrines had integrated buildings. Maggots or pupae or adult flies were found in 33.33% of sanitary latrines and all of non-sanitary latrines with the average amounts of 1.05 and 3.40 per latrine respectively. The removal rate of fecal coliform, the sedimentation rate of parasitic eggs and the mortality rate of Ascaris eggs were 90.00%, 80.61% and 95.20% on average respectively. The qualified rate of the fecal coliform of the outlet of the sanitary latrines was 41.67%, and the qualified rate of the mortality rate of Ascaris eggs was 78.13%. No living schistosome eggs were found at the outlets of latrines. For the effect of non-hazardous treatment, there was a statistically significant difference between the sanitary latrines and non-sanitary latrines. CONCLUSIONS: The latrine improvement has a good effect on non-hazardous treatment of the excrement in Yunnan Province, but the construction, application and management of sanitary latrines still need to be strengthened.