A Three-Dimensional Technique for The Visualization of Mitochondrial Ultrastructural Changes in Pancreatic Cancer Cells.

Understanding the dynamic features of the cell organelle ultrastructure, which is not only rich in unknown information but also sophisticated from a three-dimensional (3D) perspective, is critical for mechanistic studies. Electron microscopy (EM) offers good imaging depth and allows for the reconstruction of high-resolution image stacks to investigate the ultrastructural morphology of cellular organelles even at the nanometer scale; therefore, 3D reconstruction is gaining importance due to its incomparable advantages. Scanning electron microscopy (SEM) provides a high-throughput image acquisition technology that allows for reconstructing large structures in 3D from the same region of interest in consecutive slices. Therefore, the application of SEM in large-scale 3D reconstruction to restore the true 3D ultrastructure of organelles is becoming increasingly common. In this protocol, we suggest a combination of serial ultrathin section and 3D reconstruction techniques to study mitochondrial cristae in pancreatic cancer cells. The details of how these techniques are performed are described in this protocol in a step-by-step manner, including the osmium-thiocarbohydrazide-osmium (OTO) method, the serial ultrathin section imaging, and the visualization display.

Intermittent hypoxia exacerbated depressive and anxiety-like behaviors in the bleomycin-induced pulmonary fibrosis mice.

Depression and anxiety are prevalent in patients with idiopathic pulmonary fibrosis (IPF). Recent researchers reveal that intermittent hypoxia (IH) increases the severity of bleomycin (BLM)-induced lung injury. However, experimental studies dealing with anxiety- and depression-like behavior in animal models of BLM-induced pulmonary fibrosis in a combination of IH are lacking, hence, this study aimed to investigate that. In this study, 80 C57BL/6J male mice were intratracheally injected with BLM or normal saline at day0 and then exposed to IH (alternating cycles of FiO2 21 % for 60 s and FiO2 10 % for 30 s, 40 cycles/hour, 8 h/day) or intermittent air (IA) for 21 days. Behavioral tests, including open field test (OFT), sucrose preference test (SPT) and tail suspension test (TST), were detected from day22 to day26. This study found that pulmonary fibrosis developed and lung inflammation were activated in BLM-induced mice, which were potentiated by IH. Significant less time in center and less frequency of entries in the centre arena in OFT were observed in BLM treated mice, and IH exposure further decreased that. Marked decreased percent of sucrose preference in SPT, and significant increased immobility time of the TST were detected in BLM treated mice and IH widen the gaps. The expression of ionized calcium-binding adaptor molecule (Iba1) was activated in the hippocampus of BLM instillation mice and IH enlarged it. Moreover, a positive correlation between hippocampal microglia activation and inflammatory factors was observed. Our results demonstrated that IH exacerbated depressive and anxiety-like behaviors in the BLM-induced pulmonary fibrosis mice. The changes in pulmonary inflammation-hippocampal microglia activation may be a potential mechanism in this phenomenon, which can be researched in future.

Development and Validation of a Prognostic Nomogram in Lung Cancer With Obstructive Sleep Apnea Syndrome.

To analyze the prognostic factors and survival rate of lung cancer patients with obstructive sleep apnea (OSA) by nomogram. The nomogram was established by a development cohort (n = 90), and the validation cohort included 38 patients. Factors in the nomogram were identified by Cox hazard analysis. We tested the accuracy of the nomograms by discrimination and calibration, and plotted decision curves to assess the benefits of nomogram-assisted decisions. There were significant difference in sex, apnea hypopnea index (AHI), Tumor Node Metastasis (TNM), coronary heart disease, lowest arterial oxygen saturation [LSpO2 (%)], oxygen below 90% of the time [T90% (min)], the percentage of the total recorded time spend below 90% oxygen saturation (TS90%) and oxygen desaturation index (ODI4) between lung cancer subgroup and lung cancer with OSA subgroup (P < 0.05). Lung cancer patients with OSA age, AHI, TNM, cancer types, BMI and ODI4 were independent prognostic factor. Based on these six factors, a nomogram model was established. The c-index of internal verification was 0.802 (95% CI 0.767-0.885). The ROC curve analysis for the nomogram show 1-year survival (AUC = 0.827), 3-year survival (AUC = 0.867), 5-year survival (AUC = 0.801) in the development cohort were good accuracy. The calibration curve shows that this prediction model is in good agreement. Decision curve analysis (DCA) suggests that the net benefit of decision-making with this nomogram is higher, especially in the probability interval of <20% threshold. The nomogram can predict the prognosis of patients and guide individualized treatment.

Obstructive Sleep Apnea is Associated with an Increased Prevalence of Polycythemia in Patients with Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are associated with polycythemia. However, there still remain unanswered questions about the relationship between overlap syndrome (OVS), where OSA and COPD coexist, and polycythemia. Here, we aimed to establish the prevalence of polycythemia in OVS patients and to explore the impact of OSA on polycythemia. PATIENTS AND METHODS: Patients with COPD underwent overnight polysomnography (PSG), pulmonary function tests, echocardiography, and complete blood counts. All patients were ethnic Han Chinese and free of prolonged oral corticosteroid use, hematological system disease, severe systemic disease, and other sleep-disordered breathing. OVS was defined as COPD patients with an apnea-hypopnea index ≥15 events/h, and polycythemia was defined as an Hb >165 g/L in men and >160 g/L in women. RESULTS: Eight-hundred and eighty-six patients with COPD were included in the analysis. The prevalence of polycythemia was significantly higher in OVS patients than COPD-alone patients (6.4% vs 2.9%, p < 0.05). The prevalence of polycythemia increased with OSA severity (χ 2 = 7.885, p = 0.007), but not in GOLD grade 3-4 COPD patients (χ 2 = 0.190, p = 0.663). After adjusting for confounders, percentage of total sleep time with SaO2 <90% (TS90) remained independently associated with an increased odds of polycythemia (OR 1.030, 95% CI 1.015-1.046) and, with an increase in TS90, the hemoglobin increased, especially in GOLD grade 1-2 patients (p < 0.05). CONCLUSION: Patients with OVS have a higher prevalence of polycythemia than those with COPD alone, and TS90 is an independent factor for polycythemia, especially in GOLD1-2 COPD patients.

Associations between daytime and nighttime plasma orexin A levels and cognitive function in patients with obstructive sleep apnea.

The relationship between plasma orexin A (OXA) levels and cognitive function in patients with obstructive sleep apnea (OSA) remains unclear. This study aimed to evaluate associations between daytime and nighttime plasma OXA levels and cognitive function in patients with OSA. Subjects with suspected OSA underwent overnight polysomnography (PSG), Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS) assessment. Subjects were considered controls or having OSA according to the apnea-hypopnea index (AHI). Daytime and nighttime plasma OXA levels were determined by ELISA. Receiver-operating characteristics curves were used to evaluate the diagnostic value of plasma OXA levels for assessing cognitive impairment in OSA patients. One hundred and six subjects met the inclusion criteria. MoCA scores and plasma OXA concentrations were significantly lower in OSA patients than controls (p < 0.01). Patients with moderate and severe OSA had significantly lower MoCA scores than controls and mild OSA patients (p < 0.01). Daytime and nighttime OXA levels were significantly lower in OSA patients with cognitive impairment than those without cognitive impairment (p < 0.01). Both daytime and nighttime plasma OXA levels in patients with OSA were positively correlated with MoCA scores and nadir SaO2, negatively correlated with AHI, oxygen desaturation index, and percentage of time spent with an SaO2 below 90% (all p < 0.05), and not correlated with ESS scores. The optimal threshold of daytime plasma OXA to diagnose OSA with cognitive impairment was 49.34 pg/ml, with a sensitivity of 80.0% and a specificity of 74.3%. We concluded that plasma OXA concentrations might be related to cognitive function and daytime plasma OXA levels have diagnostic value for assessing cognitive impairment in OSA patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00387-4.

Intermittent hypoxia increases ROS/HIF-1α 'related oxidative stress and inflammation and worsens bleomycin-induced pulmonary fibrosis in adult male C57BL/6J mice.

Obstructive sleep apnea (OSA) has been increasingly recognized as a risk factor for idiopathic pulmonary fibrosis (IPF). The intermittent hypoxia (IH) and re-oxygenation of OSA contribute to poor outcomes of IPF, however, the potential mechanism remains unknown. Here, C57BL/6J mice were administered intratracheal injection of Bleomycin (BLM) or saline and then exposed to IH (alternating cycles of FiO2 21% for 60S and FiO2 10% for 30 s, 40 cycles/hour, 8 h/day) to mimic OSA or intermittent air (IA) for 4 days, 8 days or 21 days. This study found that pulmonary fibrosis in BLM + IH treated mice was more severe than that in BLM + IA group at day 8 and 21, but not observed at day 4. Besides, the expression of reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α),which are related to hypoxia reduced oxidative stress and inflammation, were higher in BLM + IH treated mice than BLM + IA mice, and IH increased these indexes in BLM treated mice from day 4 to day 21. Interestingly, a positive linear correlation between the HIF-1α expression and hydroxyproline (HYP) content was observed. We further found some inflammatory cells in bronchoalveolar lavage fluid were increased significantly from day 4 to 21, and there was a positive correlation between inflammation and ROS expression. Our results demonstrated that IH aggravated BLM-induced pulmonary fibrosis, and ROS/HIF-1α related oxidative stress and inflammation involved. The increase of ROS/HIF-1α related oxidative stress and inflammation may be a potential mechanism of moderate-to-severe OSA in potentiating pulmonary fibrosis of IPF, which warrants further study.

Cigarette smoking induces aberrant N6-methyladenosine of DAPK2 to promote non-small cell lung cancer progression by activating NF-κB pathway.

N6-methyladenosine (m6A) has recently emerged as an important regulatory mechanism for gene expression and aberrant m6A modification plays an important role in tumor progression. Emerging evidence has shown that aberrant m6A modification induced by cigarette smoking is involved in carcinogenesis, but whether cigarette smoking affects m6A modification and thus deteriorates to non-small cell lung cancer (NSCLC) is still unclear. Here, we identified a tumor suppressor gene-DAPK2 which was significantly associated with poor prognosis of NSCLC patients, especially in patients with a smoking history. Low levels of DAPK2 were detected in smokers and in NSCLC tissues. Cigarette smoking induced aberrant N6-methyladenosine modification of DAPK2, which resulted in decreased DAPK2 mRNA stability and expression of its mRNA and protein. This modification was mediated by the m6A "writer" METTL3 and the m6A "reader" YTHDF2. Mechanistically, we further demonstrated that DAPK2 functions as a tumor suppressor and downregulation of DAPK2 substantially enhances the proliferation and migration abilities in vitro and in vivo by activating NF-κB signaling pathway. Notably, the BAY 11-7085, a NF-κB signaling selective inhibitor, was shown to efficiently suppressed downregulation of DAPK2-induced oncogenic phenotypes of NSCLC cells. Our study reveals that cigarette smoking induces aberrant N6-methyladenosine of DAPK2 to promote NSCLC progression, which provides new insight into the mechanisms of NSCLC progression and a specific therapeutic target for NSCLC patients with a smoking history.

A Novel Prognostic and Predictive Signature for Lung Adenocarcinoma Derived from Combined Hypoxia and Infiltrating Immune Cell-Related Genes in TCGA Patients.

BACKGROUND: The hypoxia and immune status of the lung adenocarcinoma (LUAD) microenvironment appear to have combined impacts on prognosis. Therefore, deriving a prognostic signature by integrating hypoxia- and immune infiltrating cell-related genes (H&IICRGs) may add value over prognostic indices derived from genes driving either process alone. METHODS: Differentially expressed H&IICRGs (DE-H&IICRGs) were identified in The Cancer Genome Atlas transcriptomic data using limma, CIBERSORT, weighted gene co-expression network analysis, and intersection analysis. A stepwise Cox regression model was constructed to identify prognostic genes and to produce a gene signature based on DE-H&IICRGs. The potential biological functions associated with the gene signature were explored using functional enrichment analysis. The prognostic signature was externally validated in a separate cohort from the Gene Expression Omnibus database. RESULTS: Five prognostic genes associated with overall survival in LUAD were used in the DE-H&IICRG-based prognostic signature. Patients in the high-risk group had an inferior prognosis, which was validated in an independent external cohort, and had lower expression of most immune checkpoint genes. In multivariate analysis, only risk score and T stage were independent prognostic factors. Differentially expressed genes (DEGs) associated with the risk score were enriched for pathways related to cell cycle, hypoxia regulation, and immune response. TIDE analyses showed that low-risk LUAD patients might also respond better to immunotherapy. CONCLUSION: This study establishes and validates a prognostic profile for LUAD patients that combines hypoxia and immune infiltrating cell-related genes. This signature may have clinical application both for prognostication and guiding individualized immunotherapy.

Hypoxia in utero increases the risk of pulmonary hypertension in rat offspring and is associated with vasopressin type­2 receptor upregulation.

Pulmonary hypertension (PH) in newborns and adults is a disease that can lead to right heart failure and result in a shorter lifespan. PH was induced by maintaining pregnant rats in a hypoxic chamber for 4 h twice a day, from days 7­21 of pregnancy. Hypoxia was confirmed by a decrease in the partial pressure of oxygen (PaO2) and the oxygen saturation (SaO2) of arterial blood in the aorta. The body weight of newborns from hypoxic rats was ~20% decreased compared with the control newborns of normoxic rats. The vascular wall thickness/vascular diameter values of hypoxia treated pubs were increased compared with that of control newborns 7 days after birth; however, it decreased to similar levels than in the control group after 3 months, and then further decreased to significantly lower levels than in the control group at 6 months after birth. At birth, the lung tissues of newborns from hypoxic rats exhibited an increase in the levels of mRNA and proteins associated with PH such as HIF­1α, HIF­2α, V2R, TGF­ß, TNF­α, Ang­2 and α­SMA. At 3 and 6 months after birth, the levels of both V2R mRNA and protein in offspring from hypoxic rats were at least 2­fold higher, whereas the expression of all other factors decreased compared with the control offspring. By contrast, HIF­2α and Ang­2 expression levels were significantly increased in the 6­month­old control offspring from normoxic rats. V2R overexpression in pups induced by hypoxia in maternal rats was sustained until their adulthood. V2R may be a marker for detecting PH.

Clinical Courses and Outcomes of Patients with Chronic Obstructive Pulmonary Disease During the COVID-19 Epidemic in Hubei, China.

Purpose: In this study, we investigated the acute exacerbation and outcomes of COPD patients during the outbreak of COVID-19 and evaluated the prevalence and mortality of COPD patients with confirmed COVID-19. Methods: A prospectively recruited cohort of 489 COPD patients was retrospectively followed-up for their conditions during the COVID-19 pandemic from December 2019 to March 2020 in Hubei, China. In addition, the features of 821 discharged patients with confirmed COVID-19 were retrospectively analyzed. Results: Of the 489 followed-up enrolled COPD patients, 2 cases were diagnosed as confirmed COVID-19, and 97 cases had exacerbations, 32 cases of which were hospitalized, and 14 cases died. Compared with the 6-month follow-up results collected 1 year ago, in 307 cases of this cohort, the rates of exacerbations and hospitalization of the 489 COPD patients during the last 4 months decreased, while the mortality rate increased significantly (2.86% vs 0.65%, p=0.023). Of the 821 patients with COVID-19, 37 cases (4.5%) had pre-existing COPD. Of 180 confirmed deaths, 19 cases (10.6%) were combined with COPD. Compared to COVID-19 deaths without COPD, COVID-19 deaths with COPD had higher rates of coronary artery disease and/or cerebrovascular diseases. Old age, low BMI and low parameters of lung function were risk factors of all-cause mortality for COVID-19 patients with pre-existing COPD. Conclusion: Our findings imply that acute exacerbations and hospitalizations of COPD patients were infrequent during the COVID-19 pandemic. However, COVID-19 patients with pre-existing COPD had a higher risk of all-cause mortality.

Effect of Body Mass Index on Lung Function in Chinese Patients with Chronic Obstructive Pulmonary Disease: A Multicenter Cross-Sectional Study.

Objective: The aim of this study was to explain "obesity paradox" in chronic obstructive pulmonary disease (COPD) by evaluating the effect of body mass index (BMI) on lung function in Chinese patients with COPD. Methods: A total of 1644 patients diagnosed with COPD were recruited from four Chinese tertiary hospitals and were divided into four groups including underweight, normal weight, overweight and obese according to BMI classification standard. The medical data of these patients were collected and used for the multiple linear regression analyses. Results: After adjustment for age, sex, educational level, economic status, smoking status, alcohol consumption, duration of COPD history, events of acute exacerbation in previous year, hypertension, diabetes mellitus, cardiovascular disease, cerebrovascular disease and osteoporosis, BMI had a curvilinear correlation with the forced expiratory volume in the first second (FEV1) in patients with Global Initiative for Obstructive Lung Disease (GOLD) 1-2 grade (first-order coefficient ß, 0.09; 95% CI, 0.03-0.16; second-order coefficient ß, -0.002; 95% CI, -0.003--0.001; P<0.01). However, BMI had a positive correlation with FEV1 in patients with GOLD 3-4 grade (ß, 0.01; 95% CI, 0.008-0.017; P<0.01) when BMI was used as a quantitative variable. When BMI was used as a qualitative variable, only FEV1 in overweight group with GOLD 1-2 grade was significantly higher than that of normal weight group (P<0.01). Interestingly, both overweight and obese groups had higher FEV1 in GOLD 3-4 grade compared with normal weight group (ß, 0.06; 95% CI, 0.02-0.11; ß, 0.11; 95% CI, 0.04-0.18; P<0.01). The effect of BMI on predicted percentage of FEV1 (FEV1%) was similar to that of FEV1 in different GOLD grades. Conclusion: Obesity only had a protective effect on lung function in COPD patients with GOLD 3-4 grade rather than GOLD 1-2 grade. Trial Registry: ClinicalTrials.gov, No.: NCT03182309, URL: www.clinicaltrials.gov.

Obstructive Sleep Apnea Increases the Prevalence of Hypertension in Patients with Chronic Obstructive Disease.

Whether there are increased rates of chronic diseases associated with the combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) overlap syndrome (OVS) has not been determined. The purpose of this study was to assess the prevalence of five comorbidities in COPD and OVS patients. A total of 968 patients with confirmed COPD were included in this study. Participants were requested to fill out a questionnaire involving their basic information and medical history. All subjects underwent one overnight polysomnography and were then divided into an OVS group or a COPD only group according to their apnea-hypopnea index. The prevalence of hypertension, diabetes, cardiovascular disease, arrhythmia and cerebrovascular disease were compared and risk factors for comorbidities in COPD patients were identified. Compared with the COPD only group, the prevalence of hypertension was significantly higher in the OVS group, however, the prevalence rates of the other four kinds of diseases were not statistically different between the two groups. In COPD patients, the prevalence of hypertension increased with the severity of OSA and the prevalence of arrhythmia increased with airflow limitation severity. Risk factors for OSA in patients with COPD included BMI, FEV1%, Epworth Sleepiness Scale score and the Sleep Apnea Clinical Score. OSA was an independent risk factor for hypertension. The other risk factors for hypertension in COPD patients included age, BMI, CAT score and alcohol consumption. Age, lower FEV1% may be risk factors for arrhythmia. OVS patients were associated with a high prevalence rate of hypertension, while OSA was an independent risk factor for hypertension.

Effects of the excitation or inhibition of basal forebrain cholinergic neurons on cognitive ability in mice exposed to chronic intermittent hypoxia.

Cognitive impairment of obstructive sleep apnea syndrome (OSAS) patients is related to the basal forebrain (BF) cholinergic neurons. To further investigate the effect of the excitation or inhibition of BF cholinergic neurons on cognitive ability, we employed a chronic intermittent hypoxia (CIH) mice model and implanted microinjection cannulas in the BFs for targeted intervention, finally performed the behavioral experiments and examined immunohistochemistry and biochemical changes in the BFs. The results showed that (1) CIH induced cognitive decline in mice. (2) The excitation of BF cholinergic neurons attenuated cognitive decline, while the inhibition of these neurons aggravated cognitive impairment. (3) Microinjection of adenosine into the BF aggravated cognitive decline, while caffeine improved cognitive ability. (4) CIH induced BF cholinergic neuron injury in mice. (5) The excitation of BF cholinergic neurons alleviated cholinergic neuron injury, while the inhibition of these neurons aggravated this injury. (6) Microinjection of adenosine into the BF aggravated cholinergic neuron injury, while caffeine alleviated this injury. (7) CIH induced endoplasmic reticulum stress, oxidative stress and inflammatory responses in the BFs of mice. (8) The excitation of BF cholinergic neurons mitigated endoplasmic reticulum stress, oxidative stress and inflammatory responses in the BF in mice, while the inhibition of BF cholinergic neurons worsened these responses in the BF. (9) Microinjection of adenosine into the BF aggravated endoplasmic reticulum stress, oxidative stress and the inflammatory response, while caffeine alleviated these responses. This work indicates that CIH induces BF cholinergic neuron injury through multiple pathways, including endoplasmic reticulum stress, oxidative stress and the inflammatory response, thereby leading to cognitive dysfunction in mice. BF cholinergic neurons play a vital role in these pathways, thus reducing cholinergic neuron injury and restoring cognitive function in mice. Adenosine, which is an upstream modifier of acetylcholine, also plays an important role in altering cognitive ability.

Chronic intermittent hypoxia vs chronic continuous hypoxia: Effects on vascular endothelial function and myocardial contractility.

BACKGROUND AND AIM: Both chronic intermittent hypoxia (CIH) and chronic continuous hypoxia (CCH) are risk factors for cardiovascular disease, which are associated with cardiac systolic function and associated with dysfunction of endothelia and coagulation-fibrinolysis system in the vasculature. However, the different effects of these two hypoxic models are not fully understood. In our study, we systemically compared the effects of CIH and CCH on cardiac function and related factor levels in serum using rat model. METHODS: Forty-five male Sprague-Dawley rats were randomly divided into the normoxia control (NC), CIH and CCH groups. The rat CIH and CCH models were established, then the blood and tissue samples were collected to analyze the function of endothelium and the coagulation-fibrinolysis system. Also, the ultrasound cardiogram was performed to directly assess myocardial contractility. RESULTS: Both CIH and CCH significantly decreased the NO, eNOS, P-eNOS and AT-III levels in the rat serum but significantly increased the levels of ET-1, vWF, COX-2, NF-κB, FIB, FVIII and PAI-1 in the rat serum (P < 0.05). The expression of ET-1, VWF and ICAM-1 in CIH group were higher than CCH group (P < 0.05), however, the expression of CD62p was increased in CCH group but not in CIH group. The expression of t-PA in CIH group were lower than CCH group (P < 0.05), but there were no significant differences in CCH group and NC group (P > 0.05). Using transmission electron microscope, we found that the mitochondrial ultrastructure of thoracic aorta endothelial cells in CIH and CCH group were damaged. Moreover, the myocardial contractility in CIH and CCH group were significantly decreased compared with NC group. CONCLUSION: Our results suggested that CIH and CCH could cause endothelial dysfunction, dysfunction of the coagulation-fibrinolysis system and decreasing of myocardial contractility. Compared with CCH, CIH has greater effect on vasoconstriction and adhesion of vascular endothelial cells, and stronger procoagulant effect.

Linc00467 promotes lung adenocarcinoma proliferation via sponging miR-20b-5p to activate CCND1 expression.

BACKGROUND: Recently, numerous studies have demonstrated the emerging role of long non-coding RNAs (lncRNAs) in human cancers. Linc00467 is a newly defined lncRNA and was reported to promote cell survival in neuroblastoma. However, the function of linc00467 in lung cancer is still unclear. MATERIAL AND METHODS: We analyzed linc00467 expression and survival data derived from The Cancer Genome Altas lung adenocarcinoma (LUAD) dataset as well as in collected LUAD tissues. Then, we silenced linc00467 expression in two lung cancer cell lines using small interfering RNAs and explored the effect of linc00467 knockdown on cell growth in vitro and in vivo. Moreover, we revealed a novel target gene of linc00467 and elucidated the underlying competitive endogenous RNA regulatory mechanism in lung cancer cells. RESULTS: Our data suggested that linc00467 expression was elevated in LUAD tissues and correlated with overall survival of LUAD patients. Linc00467 knockdown resulted in reduced proliferation rate in lung cancer cells. Furthermore, we elucidated that linc00467 promoted CCND1 expression in lung cancer cells via functioning as a molecular sponge for miR-20b-5p. CONCLUSION: Linc00467/miR-20b-5p/CCND1 signaling pathway may provide new insights into lung cancer treatment.

The role of gonadal hormones in the hypoglossal discharge activity of rats exposed to chronic intermittent hypoxia.

OBJECTIVE: The role of gonadal hormones in chronic intermittent hypoxia (CIH)-evoked hypoglossal nerve (XII) neuroplasticity has not been thoroughly studied. The purpose of this study was to reveal the effects of gonadal hormone concentration variations on the XII discharge activity of rats exposed to CIH and the corresponding relationship with 5-hydroxytryptamine (5-HT). METHODS: This study employed five groups of female rats and six groups of male rats. Gonadal hormone levels were modified through gonadal resection and daily supplementation with gonadal hormones in rats of both sexes. Rats in the CIH groups were exposed to an additional 4 weeks of CIH once the operative incision for gonadectomy had healed. Finally, XII spontaneous discharge activities were recorded, and serum estradiol, testosterone and 5-HT concentrations were detected by ELISA. RESULTS: Among the female rats, the normal estradiol level groups expressed XII neuroplasticity, while the low estradiol level group failed to express this phenomenon. XII neuroplasticity was related to the serum estradiol concentration. In the male rats, XII neuroplasticity was successfully evoked in the normal testosterone level group but was suppressed in the low testosterone level group and aromatase inhibitor group. XII neuroplasticity was not significantly related to serum testosterone concentrations. Both estradiol and testosterone concentrations were related to 5-HT concentrations. CONCLUSIONS: This is the first study to analyze the effects of gonadal hormones on XII neuroplasticity in both female and male rats. The results suggest that the estradiol level is related to XII neuroplasticity rather than the testosterone level, and testosterone may indirectly adjust XII neuroplasticity by converting to estradiol. Estradiol and testosterone levels are related to 5-HT levels in the respective genders.

The Screening Value Of ESS, SACS, BQ, And SBQ On Obstructive Sleep Apnea In Patients With Chronic Obstructive Pulmonary Disease.

Objective: To compare the performance of Epworth sleepiness scale (ESS), sleep apnea clinical score (SACS), Berlin questionnaire (BQ), and STOP-BANG questionnaire (SBQ) in screening for obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 431 patients were analyzed. All subjects completed lung function test, ESS, SACS, BQ, and SBQ survey and overnight polysomnography (PSG). According to lung function and PSG results, participants were divided into COPD with OSA group (OVS, AHI ≥5) and without OSA group (AHI <5). The value of ESS, SACS, BQ, and SBQ was compared in predicting OSA in patients with COPD by receiver-operating characteristic (ROC) curve statistics. Results: Of the 431 subjects, there were 96 cases in COPD without OSA group, and 335 cases in OVS group including 183, 96, and 56 cases of COPD combined with mild, moderate or severe OSA. In predicting different degrees of severity of OSA in patients with COPD, the value of ESS was poor with all the values of area under the curve (AUC) < 0.7. SACS and BQ had moderate predictive value in screening for severe OSA with the value of AUC of 0.750, 0.735 respectively. However, the SBQ performed best in predicting various degrees of OSA. For screening mild OSA (AHI ≥5), the ROC statistics recommended the cut-off score of SBQ >2 was considered high risk of OSA; the sensitivity, specificity, and AUC were 92.8%, 40.6%, and 0.723 respectively, the odds ratio (OR) was 2.161. When AHI ≥15, AUC for SBQ was 0.737. In predicting severe OSA (AHI ≥30), the ROC curve showed cut-off point, sensitivity, specificity, and AUC for SBQ was >4, 66.1%, 82.1%, and 0.824 respectively; the positive and negative likelihood ratio was 3.70, 0.41 separately, the OR was 2.977. Conclusion: SBQ performed better than ESS, SACS, and BQ in predicting OSA in patients with COPD.

Recurrent, late-onset pleural effusions in elderly patients receiving pacemaker therapy.

Late-onset pacemaker-related pleural effusions (PEs) are rare and are often misdiagnosed with other entities. Our study aimed to detail the clinical features and management of PEs long after pacemaker insertion.We conducted a review of 6 consecutive elderly patients with PEs, who had undergone a new pacemaker insertion from September 2014 to January 2017. Also, the clinical characteristics and therapeutic courses of PEs were summarized.Two cases involved fluids after the first implantations, with pacing durations of 3 and 7 months. Two other cases developed PEs 3 or 4 months after the first replacement, with pacing durations of 6 and 11 years. Another 2 cases developed PEs 3 or 5 months following the second replacement, with total pacing durations of 16 and 18 years, respectively. The average interval was 4.17 months for the 6 cases from the time of the new pacemaker insertion to the occurrence of PEs. During the course, they had to be hospitalized repeatedly for thoracenteses because conventional treatments had only short-term effects. After the pacing settings were adjusted, PEs in all cases disappeared gradually. No patients were readmitted for PEs during the median follow-up period of 13 months.For elderly patients following implantation of a new pacemaker, PEs should be considered due to improper pacing settings, and corresponding adjustments to the device should be made.