Air pollution enhance the progression of restrictive lung function impairment and diffusion capacity reduction: an elderly cohort study.

BACKGROUND: Some evidences have shown the association between air pollution exposure and the development of interstitial lung diseases. However, the effect of air pollution on the progression of restrictive ventilatory impairment and diffusion capacity reduction is unknown. This study aimed to evaluate the effects of long-term exposure to ambient air pollution on the change rates of total lung capacity, residual volume, and diffusion capacity among the elderly. METHODS: From 2016 to 2018, single-breath helium dilution with the diffusion capacity of carbon monoxide was performed once per year on 543 elderly individuals. Monthly concentrations of ambient fine particulate matters (PM2.5) and nitric dioxide (NO2) at the individual residential address were estimated using a hybrid Kriging/Land-use regression model. Linear mixed models were used to evaluate the association between long-term (12 months) exposure to air pollution and lung function with adjustment for potential covariates, including basic characteristics, indoor air pollution (second-hand smoke, cooking fume, and incense burning), physician diagnosed diseases (asthma and chronic airway diseases), dusty job history, and short-term (lag one month) air pollution exposure. RESULTS: An interquartile range (5.37 ppb) increase in long-term exposure to NO2 was associated with an additional rate of decline in total lung volume (- 1.8% per year, 95% CI: - 2.8 to - 0.9%), residual volume (- 3.3% per year, 95% CI: - 5.0 to - 1.6%), ratio of residual volume to total lung volume (- 1.6% per year, 95% CI: - 2.6 to - 0.5%), and diffusion capacity (- 1.1% per year, 95% CI: - 2.0 to - 0.2%). There is no effect on the transfer factor (ratio of diffusion capacity to alveolar volume). The effect of NO2 remained robust after adjustment for PM2.5 exposure. CONCLUSIONS: Long-term exposure to ambient NO2 is associated with an accelerated decline in static lung volume and diffusion capacity in the elderly. NO2 related air pollution may be a risk factor for restrictive lung disorders.

Trajectory mapping of the early Drosophila germline reveals controls of zygotic activation and sex differentiation.

Germ cells in Drosophila melanogaster are specified maternally shortly after fertilization and are transcriptionally quiescent until their zygotic genome is activated to sustain further development. To understand the molecular basis of this process, we analyzed the progressing transcriptomes of early male and female germ cells at the single-cell level between germline specification and coalescence with somatic gonadal cells. Our data comprehensively cover zygotic activation in the germline genome, and analyses on genes that exhibit germline-restricted expression reveal that polymerase pausing and differential RNA stability are important mechanisms that establish gene expression differences between the germline and soma. In addition, we observe an immediate bifurcation between the male and female germ cells as zygotic transcription begins. The main difference between the two sexes is an elevation in X Chromosome expression in females relative to males, signifying incomplete dosage compensation, with a few select genes exhibiting even higher expression increases. These indicate that the male program is the default mode in the germline that is driven to female development with a second X Chromosome.

circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response.

Deep sequencing technologies have revealed the once uncharted non-coding transcriptome of circular RNAs (circRNAs). Despite the lack of protein-coding potential, these unorthodox yet highly stable RNA species are known to act as critical gene regulatory hubs, particularly in malignancies. However, their mechanistic implications in tumor outcome and translational potential have not been fully resolved. Using RNA-seq data, we profiled the circRNAomes of tumor specimens derived from oral squamous cell carcinoma (OSCC), which is a prevalently diagnosed cancer with a persistently low survival rate. We further catalogued dysregulated circRNAs in connection with tumorigenic progression. Using comprehensive bioinformatics analyses focused on co-expression maps and miRNA-interaction networks, we delineated the regulatory networks that are centered on circRNAs. Interestingly, we identified a tumor-associated, pro-tumorigenic circRNA, named circFLNB, that was implicated in maintaining several tumor-associated phenotypes in vitro and in vivo. Correspondingly, transcriptome profiling of circFLNB-knockdown cells showed alterations in tumor-related genes. Integrated in silico analyses further deciphered the circFLNB-targeted gene network. Together, our current study demarcates the OSCC-associated circRNAome, and unveils a novel circRNA circuit with functional implication in OSCC progression. These systems-based findings broaden mechanistic understanding of oral malignancies and raise new prospects for translational medicine.

CHA2DS2-VASc scores predict major adverse cardiovascular events in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) frequently experience concurrent comorbidities; therefore, risk assessment for major adverse cardiovascular events (MACEs) is very important. OBJECTIVES: We explored the association between COPD and risk of MACEs with three common clinical events: acute myocardial infarction (AMI), ischemic stroke (IS), and cardiovascular death (CVD). METHODS: We evaluated the predictive value of the CHA2DS2-VASc score (congestive heart failure [C], hypertension [H], age [A], diabetes [D], stroke [S], and vascular disease [VASc]) for MACEs in COPD patients. In this observational study, we retrospectively reviewed the records of 29 258 patients with COPD between 2005 and 2009 in relation to MACE risk using the CHA2DS2-VASc score. We calculated the hazard ratios (HR) and 95% confidence intervals (CI) using a significance level of .05. RESULTS: Patients with COPD had significantly (P < .001) increased risk of MACEs, and a high prevalence of CHA2DS2-VASc scores ≥ 6, predicting MACEs (16.1%), AMI (3.3%), IS (8.7%), and CVD (4.0%). A good discrimination was found for MACEs, IS events, and CVD events (AUC = 0.740, 0.739, and 0.778, respectively) but poorer discrimination for AMI events (AUC = 0.697). CONCLUSION: Early lifestyle modifications and antithrombotic therapy may be essential for COPD patients at a high risk of MACEs, that is, those with CHA2DS2-VASc scores ≥ 6.

Intravitreal administration of bevacizumab in the treatment of choroidal metastasis in a patient with erlotinib-failed pulmonary adenocarcinoma.

Choroidal metastasis is uncommon and usually identified in a relatively advanced cancer status. The median survival after diagnosing choroid metastasis in lung cancer patients was only 1.9 months. Once failed to systemic treatment, there was no effective local treatment for saving visual acuity. The off-label use of intravitreal bevacizumab was popular in treating VEGF-mediated chorioretinal diseases worldwide. We here demonstrate a dramatic and durable response to intravitreal bevacizumab. Unlike the previous similar reports, our patient had failed both first- and second-line therapies.