Retracted: Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury.

This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Xiao-Bin Zhang, Gong-Ping Chen, Mao-Hong Huang, Xiang-Xing Chen, Feng-Fu Zhan, Xiu-Zhen He, Ling Cai, Hui-Qing Zeng Med. Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury. Med Sci Monit, 2022; 28: e936760. DOI: 10.12659/MSM.936760.

MiR-210-3p enhances intermittent hypoxia-induced tumor progression via inhibition of E2F3.

PURPOSE: Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which is related to tumorigenesis and progression. Although micro-ribonucleic acid-210-3p (miR-210-3p) is correlated with hypoxia-induced tumor development, its role in the relationship between IH and tumor function remains poorly understood. The present work focused on elucidating the molecular mechanism through which miR-210-3p drives tumor progression under IH. METHODS: MiR-210-3p levels were quantified within tumor samples from patients with lung adenocarcinoma who had or did not have OSA. Correlations between miR-210-3p and polysomnographic variables were analyzed. For in vitro experiments, miR-210-3p was inhibited or overexpressed via transfection under IH conditions. Cell viability, growth, invasion and migration assays were carried out. For in vivo modeling of IH using mouse xenografts, a miR-210-3p antagomir was intratumorally injected, tumor biological behaviors were evaluated, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry and western blot were carried out for detecting miR-210-3p and E2F transcription factor 3 (E2F3) expression. RESULTS: For patients with lung adenocarcinoma and OSA, high miR-210-3p levels showed positive relation to polysomnographic variables, such as oxygen desaturation index, apnea-hypopnea index, and proportion of total sleep time with oxygen saturation in arterial blood < 90%. IH enhanced tumor viability, proliferation, migration, and invasion, downregulated E2F3 expression, and increased miR-210-3-p levels. miR-210-3p overexpression induced similar changes. These changes were reversed by miR-210-3p inhibition in vitro or miR-210-3p antagomir through intratumoral injection in vivo. CONCLUSIONS: IH-induced tumor development is driven through miR-210-3p by E2F3 suppression. MiR-210-3p represents a potential therapeutic target among patients with concomitant cancer and OSA.

Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury.

BACKGROUND As a novel pathophysiological characteristic of obstructive sleep apnea, intermittent hypoxia (IH) contributes to human renal tubular epithelial cells impairment. The underlying pathological mechanisms remain unrevealed. The present study aimed to evaluate the influence of Bcl-2 19-kDa interacting protein 3 (BNIP3)-mediated mitophagy on IH-induced renal tubular epithelial cell impairment. MATERIAL AND METHODS Human kidney proximal tubular (HK-2) cells were exposed to IH condition. IH cycles were as follows: 21% oxygen for 25 min, 21% descended to 1% for 35 min, 1% oxygen sustaining for 35 min, and 1% ascended to 21% for 25 min. The IH exposure lasted 24 h with 12 cycles of hypoxia and re-oxygenation. Both the siBNIP3 and BNIP3 vector were transfected to cells. Cell viability and apoptosis, mitochondrial morphology and function, and mitophagy were detected by cell counting kit-8, flow cytometry and TUNEL staining, transmission electron microscopy, western blotting, and immunofluorescence, respectively. RESULTS In the IH-induced HK-2 cells, inhibition of BNIP3 further aggravated mitochondrial structure damage, and decreased mitophagy level, leading to increased cell apoptosis and decreased cell viability. While overexpression of BNIP3 enhanced mitophagy, which protected mitochondrial structure, it can decrease cell death in HK-2 cells exposed to IH. CONCLUSIONS The present study showed that BNIP3-mediated mitophagy plays a protective role against IH-induced renal tubular epithelial cell impairment.

Correction to: Telmisartan attenuates kidney apoptosis and autophagy-related protein expression levels in an intermittent hypoxia mouse model.

In the article that appeared on Page: 341-348, Vol 23 (15 September 2018) of the Sleep and breathing [1], one error was discovered in Figure 3. The picture of Normoxia and CIH in 100X is the same one. The corrected version of Figure 3 is presented here.

Telmisartan attenuates kidney apoptosis and autophagy-related protein expression levels in an intermittent hypoxia mouse model.

PURPOSE: Obstructive sleep apnea (OSA) is associated with renal impairs. As a novel pathophysiological hallmark of OSA, chronic intermittent hypoxia (CIH) enhances apoptosis and autophagy. The present study aims to evaluate the effect of telmisartan on CIH-induced kidney apoptosis and autophagy in a mouse model of OSA. MATERIALS AND METHODS: Mice were randomly allocated to normoxia, CIH, and CIH+telmisartan groups (n = 12 in each group). The CIH exposure duration was 12 weeks. Mice in the CIH+telmisartan group received telmisartan administration. The terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and western blotting of Bax and cleaved caspase-3 were conducted for evaluating apoptosis in kidney tissue. While the autophagy-related proteins, beclin-1 and LC3, were also observed via western blotting. RESULTS: The percentage of apoptotic cell in the CIH group was significantly higher than that of normoxia group; meanwhile, Bax and cleaved caspase-3 protein levels were increased in the CIH group than those of normoxia group (all p < 0.05). Compared with the normoxia group, mice in the CIH group had greater autophagy-related proteins (beclin-1 and LC3) expression. When compared to the CIH group, both the renal apoptosis and autophagy in the CIH+telmisartan group were decreased. CONCLUSION: The CIH accelerates renal apoptosis and autophagy levels. Telmisartan ameliorating those levels suggests that it might prevent renal impairs from the CIH in OSA patients.

High-sensitivity cardiac troponin T in obstructive sleep apnea patients without cardiovascular diseases: Efficacy of CPAP treatment.

The aims of this article were to determine the levels of serum high-sensitivity cardiac troponin T (hs-cTnT) in obstructive sleep apnea (OSA) patients without cardiovascular disease (CVD) and to assess the efficacy of continuous positive airway pressure (CPAP). Snorers referred for polysomnography (PSG) for the investigation of OSA were eligible and hs-cTnT levels measured in our pilot study. Hs-cTnT was measured again after 3 months of CPAP treatment in participants with severe OSA. A total of 93 participants recruited after PSG. When compared with simple snoring group, severe OSA group had comparable higher hs-cTnT (7.5 ± 3.0 vs. 5.0 ± 2.1; p < 0.05). Hs-cTnT was positively correlated with apnea hypopnea index, and oxygen desaturation index ( r = 0.283, 0.282; p = 0.006, 0.006, respectively). Hs-cTnT levels were not significantly altered in 28 individuals who received 3 months of CPAP treatment (8.4 ± 2.4 vs.7.6 ± 2.1; p = 0.064). Elevated hs-cTnT levels were observed in severe OSA patients without CVD, and CPAP treatment had no influence on this levels.

Vascular endothelial growth factor levels in patients with obstructive sleep apnea: a meta-analysis.

Published articles regarding the blood levels of vascular endothelial growth factor (VEGF) in obstructive sleep apnea (OSA) patients are contradictory. The objective of this study was to explore whether VEGF levels is high or not in OSA subjects via quantitatively statistical analysis. The electronic databases of Pubmed, Web of Science, EMBASE were systematic searched. The VEGF levels and clinical characteristics of participants between OSA group and control group were extracted for analysis. Weighted mean difference (WMD) or standard mean difference (SMD) with 95 % confidence interval (CI) was calculated by fixed effects or random effects model. Appropriate statistical software was employed for data synthesis. Totaling 15 articles with 697 participants were included in this study. Pooled meta-analysis showed that blood VEGF concentrations were significantly higher in OSA patients than in control subjects (SMD 1.89, 95 % CI 0.92-2.87, p = 0.000). Subgroup analysis demonstrated that when compared with control group, OSA patients with age ≥50 years (SMD 2.54, 95 % CI 1.28-3.80, p = 0.000), apnea hypopnea index ≥30 events/h (SMD 2.47, 95 % CI 1.20-3.73, p = 0.000) had higher VEGF levels. Compared with control subjects, OSA patients had an elevated VEGF in serum (SMD 3.55, 95 % CI 1.82-5.28, p = 0.000) rather than in plasma. High blood VEGF concentrations were observed in OSA patients, particularly in the older and more serious patients.

Erythropoietin levels in patients with sleep apnea: a meta-analysis.

Currently available data regarding the blood levels of erythropoietin (EPO) in sleep apnea (SA) patients are contradictory. The aim of the present meta-analysis was to evaluate the EPO levels in SA patients via quantitative analysis. A systematic search of Pubmed, Embase, and Web of Science were performed. EPO levels in SA group and control group were extracted from each eligible study. Weight mean difference (WMD) or Standard mean difference (SMD) with 95% confidence interval (CI) was calculated by using fixed-effects or random effect model analysis according to the degree of heterogeneity between studies. A total of 9 studies involving 407 participants were enrolled. The results indicated that EPO levels in SA group were significantly higher than that in control group (SMD 0.61, 95% CI 0.11-1.11, p = 0.016). Significantly higher EPO levels were found in patients with body mass index <30 kg/m2, and cardiovascular complications in the subsequent subgroup analysis (both p < 0.05). High blood EPO levels were found in SA patients in the present meta-analysis.

Erectile Dysfunction and Sexual Hormone Levels in Men With Obstructive Sleep Apnea: Efficacy of Continuous Positive Airway Pressure.

In this study, the prevalence of erectile dysfunction (ED) and serum sexual hormone levels were evaluated in men with obstructive sleep apnea (OSA). In these patients, the efficacy of continuous positive airway pressure (CPAP) was determined. The 207 men (mean age 44.0 ± 11.1 years) enrolled in the study were stratified within four groups based on their apnea-hypopnea index score: simple snoring (n = 32), mild OSA (n = 29), moderate OSA (n = 38), and severe OSA (n = 108). The International Index of Erectile Dysfunction-5 (IIEF-5) score was obtained from each patient, and blood samples for the analysis of sexual hormones (prolactin, luteotropin, follicle-stimulating hormone, estradiol, progestin, and testosterone) were drawn in the morning after polysomnography. The IIEF-5 test and serum sexual hormone measurements were repeated after 3 months of CPAP treatment in 53 men with severe OSA. The prevalence of ED was 60.6 % in OSA patients overall and 72.2 % in those with severe OSA. Compared with the simple snoring group, patients with severe OSA had significantly lower testosterone levels (14.06 ± 5.62 vs. 17.02 ± 4.68, p = .018) and lower IIEF-5 scores (16.33 ± 6.50 vs. 24.09 ± 1.94, p = .001). The differences in the other sexual hormones between groups were not significant. After 3 months of CPAP treatment, there were no significant changes in sexual hormone levels, but the IIEF-5 score had improved significantly (18.21 ± 4.05 vs. 19.21 ± 3.86, p = .001). Severe OSA patients have low testosterone concentration and high ED prevalence. IIEF-5 scores increased significantly after CPAP treatment, but there was no effect on serum testosterone levels.

Efficacy of positive airway pressure on brain natriuretic peptide in patients with heart failure and sleep-disorder breathing: a meta-analysis of randomized controlled trials.

OBJECTIVE: Positive airway pressure (PAP) has been recognized as an effective therapeutic option for sleep-disordered breathing (SDB) in patients with heart failure (HF), and it can improve left ventricular function. Whether PAP can ameliorate serum brain natriuretic peptide (BNP) levels, a biomarker of HF, is controversial. The purpose of the present study was to quantitatively assess the efficacy of PAP on BNP in patients with HF and SDB. METHODS: A systematic search of PubMed, Embase, Web of Science and Cochrane library identified six randomized controlled trials (RCTs), in which PAP was compared with medical therapy, subtherapeutic PAP or different types of PAP. The data of BNP were extracted and pooled into meta-analysis using STATA 12.0. RESULTS: Totally 6 RCT studies (7 cohorts) with 222 patients were enrolled into analysis. The quality of each study was high and the heterogeneity (I(2) = 58.1%) was noted between studies. A significant reduction of BNP was observed after PAP treatment in patients with HF and SDB (SMD -0.517, 95% CI -0.764 to -0.270, z = 4.11, p = 0.000). CONCLUSION: Our meta-analysis of RCTs demonstrated that PAP elicits significant reduction of BNP in patients with HF and SDB.

Monocular endoscope 6-DoF tracking with constrained evolutionary stochastic filtering.

Monocular endoscopic 6-DoF camera tracking plays a vital role in surgical navigation that involves multimodal images to build augmented or virtual reality surgery. Such a 6-DoF camera tracking generally can be formulated as a nonlinear optimization problem. To resolve this nonlinear problem, this work proposes a new pipeline of constrained evolutionary stochastic filtering that originally introduces spatial constraints and evolutionary stochastic diffusion to deal with particle degeneracy and impoverishment in current stochastic filtering methods. With its application to endoscope 6-DoF tracking and validation on clinical data including more than 59,000 endoscopic video frames acquired from various surgical procedures, the experimental results demonstrate the effectiveness of the new pipeline that works much better than state-of-the-art tracking methods. In particular, it can significantly improve the accuracy of current monocular endoscope tracking approaches from (4.83 mm, 10.2∘) to (2.78 mm, 7.44∘).

Gorham-Stout syndrome: A chylothorax disease with bony destruction: A case report.

RATIONALE: Gorham-Stout syndrome is a sporadic condition characterized by a tumor-like lesion with extensive osteolysis, severe symptoms, and a poor prognosis. Poor prognostic indicators include osteolytic lesions of the spine and pleura effusion. PATIENT CONCERNS: A 67-year-old Chinese man with five months history of chest tightness presented to our institution with aggravated shortness of breath. Ultrasonography demonstrated hydrothorax on the right side. The patient's imaging studies (computerized tomography [CT] scan, magnetic resonance imaging, and positron emission tomography [PET]/CT) revealed osteolytic lesions (the skull, several spines, several ribs, both shoulder blades, and the pelvis). DIAGNOSES: Gorham-Stout syndrome. (4) Interventions: We advised the patient to follow a low-fat diet. On the patient, we performed a superior vena cava angiography. The injection of zoledronic acid was used to prevent bone loss. OUTCOMES: We found resolution of chylothorax after a low-fat diet, superior vena cava angiography and injection of zoledronic acid. LESSONS: The possibility of Gorham -Stout syndrome should be ruled out in patients with clinical chylothorax. The relief of chylothorax requires comprehensive treatment.

Intermittent Hypoxia Inhibits Hepatic CYP1a2 Expression and Delays Aminophylline Metabolism.

Purpose: In this study, we aimed to determine the effects of intermittent hypoxia (IH) on hepatic cytochrome P450 1A2 (CYP1A2) expression and the pharmacokinetics of CYP1A2-mediated aminophylline and warfarin in vitro and in a rabbit model of obstructive sleep apnea. Materials: Human normal liver (LO-2) cells were exposed to 30 min each of 1%, 1-21%, 21%, and 21-1% O2, and then, CYP1A2 expression and drug concentrations were analyzed. We compared the pharmacokinetic parameters of drugs administered to normoxic rabbits and those exposed to 10 min of IH during which the oxygen level fluctuated from 21% to 8%-10% (n = 10 per group). Result: s. The expression of CYP1A2 protein in vitro was significantly reduced in the IH compared with the normoxic cells (0.56 ± 0.11 vs. 1.27 ± 0.17, p < 0.001). Aminophylline was more abundant in cell culture supernatants after 48 h of IH than in those under normoxia. The T 1/2, AUC0-24 h, and Ke values for aminophylline were significantly higher in the IH group. Conclusion: Intermittent hypoxia inhibits hepatic CYP1A2 expression and delays aminophylline metabolism, suggesting that the impact of IH on the expression of CYP enzymes should be closely monitored in clinical practice.

Clinical Characteristics of COVID-19 Patients' Postvaccination.

To investigate the clinical characteristic of domestic coronavirus disease 2019 (COVID-19) patients after vaccination campaign conducted in China. According to vaccination status and months from first vaccine dose to infection detection, patients were divided into unvaccinated, <3 months, 3-6 months, and >6 months groups. The information of demographic and clinical characteristics, laboratory and thoracic computed tomography (CT) findings, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid and IgM, IgG antibodies was retrospectively collected. Therapeutic approaches, temperature-normalizing and viral shedding times, outcomes were also summarized. SARS-CoV-2 antibody levels were further analyzed based on the other following variables: time from second vaccine dose to infection, vaccine dose, the interval from the first to the second dose, and vaccine brand. Among 208 COVID-19 patients, 13 (6.28%) were unvaccinated. No significant differences in demographic and clinical characteristics, laboratory and CT findings, and SARS-CoV-2 nucleic acid loads were detected between groups (all p > 0.05). In comparison with the unvaccinated group, the median SARS-CoV-2 IgG levels were noticeably increased in those vaccinated groups (0.603 in unvaccinated, 15.925 in <3 months, 14.04 in 3-6 months, and 4.94 in >6 months, respectively, p < 0.05). However, SARS-CoV-2 IgG levels were not altered between groups divided based on the other variables. Vaccination does not affect the clinical characteristics in COVID-19 patients. COVID-19 patients with vaccination have high SARS-CoV-2 IgG levels. Underscore the necessity of rapid implementation of vaccination campaigns can be speculated.

Use of low molecular weight heparin and hemoglobin fall in COVID-19 patients: A STROBE-compliant study.

In patients with coronavirus disease 2019 (COVID-19), anticoagulation was suggested as a mitigating strategy. However, little research has been conducted on the adverse consequences of anticoagulant medication. This study aimed to investigate the adverse effect of low molecular weight heparin (LMWH) on hemoglobin fall in COVID-19 treatment. The electronic medical records of COVID-19 patients with pneumonia were collected (including clinical characteristics, vaccination status, complete blood count, coagulation profile, inflammatory cytokines, serum biochemical indicators, and computerized tomography imaging score). Whether they received LMWH, patients were divided into the LMWH group and the control group. Count data were represented as frequency distribution, and a 2-tailed test was used to compare the 2 groups. Spearman rank correlation was used to evaluate the interrelation between changes in hemoglobin and LMWH. The confounding factors were excluded by logistic regression analysis. A total of 179 COVID-19 pneumonia patients were enrolled (81 in the LMWH group and 98 in the control group). The change in hemoglobin was -6.0g/L (IQR -10.8 to 1.0) in the LMWH group and -2.0g/L (IQR -7.0 to 4.0) in the control group (P < .001, between-group difference, -5.0 g/L; 95% confidence interval, -7.0 to -3.0, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). The results of multivariate regression analysis showed that after adjusting for confounding factors, LMWH use was not associated with a decrease in hemoglobin (P > .05). In nonsevere COVID-19 patients with pneumonia, the preventive use of LMWH did not lower hemoglobin.

Diagnostic value of bronchoalveolar lavage fluid cryptococcal antigen-lateral flow immunochromatographic assay for pulmonary cryptococcosis in non-HIV patients.

BACKGROUND: The aim of this study was to investigate the diagnostic value of cryptococcal antigen-lateral flow immunochromatographic assay (CrAg-LFA) in bronchoalveolar lavage fluid (BALF) of patients with pulmonary cryptococcosis (PC). METHODS: A total of 308 patients were divided into the PC group (n = 72) and the non-PC group (n = 236). The clinical data, pathogen detection, radiological imaging, and the detection of the cryptococcal antigen in blood and BALF samples were analyzed. RESULTS: The sensitivity, specificity, positive, and negative predicted values of CrAg-LFA in the serum were 75.0%, 99.6%, 98.2%, and 92.9%, respectively, while those in the BALF were 93.1%, 100.0%, 100.0%, and 97.9%, respectively. The sensitivity of the CrAg-LFA in BALF was significantly higher than that in the serum of the patients in the PC group (P < 0.05). CONCLUSION: CrAg-LFA has a higher diagnostic value for PC when analyzing BALF samples compared to serum samples.

Atorvastatin attenuates intermittent hypoxia-induced myocardial oxidative stress in a mouse obstructive sleep apnea model.

Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), is associated with various cardiovascular diseases. In the present study, we assessed the effect of the lipid reducing agent atorvastatin on CIH-induced myocardial oxidative stress and apoptosis in a mouse OSA model. Forty-eight C57BL/6J mice were evenly divided among normoxia + vehicle, normoxia + atorvastatin, CIH + vehicle, and CIH + atorvastatin groups. CIH consisted of a hypoxia-reoxygenation cycle in which oxygen concentrations fluctuated from 21% to 6% and back over two minutes for 8 hours each day (30 events/hour). CIH exposure continued for 12 weeks. Atorvastatin (5 mg/kg) was administered from week 6 through the end of the experiment. CIH increased malondialdehyde levels and decreased superoxide dismutase activity, total antioxidant capacity, and nuclear factor erythroid 2-related factor 2 levels in cardiac tissue, indicating a reduction in antioxidant activity. Atorvastatin significantly reversed those effects (p < 0.05). CIH also increased B-cell lymphoma 2-associated protein X and cleaved caspased-3 levels as well as the myocardial apoptotic rate, as indicated by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Atorvastatin had no effect on those changes (p > 0.05). Thus, atorvastatin administration exerts antioxidant but not anti-apoptotic effects after CIH and may therefore have therapeutic potential in OSA patients with cardiovascular comorbidities.

Risk factors for mortality of coronavirus disease-2019 (COVID-19) patients in two centers of Hubei province, China: A retrospective analysis.

PURPOSE: Since the outbreak in late December 2019 in Wuhan, China, coronavirus disease-2019 (COVID-19) has become a global pandemic. We analyzed and compared the clinical, laboratory, and radiological characteristics between survivors and non-survivors and identify risk factors for mortality. METHODS: Clinical and laboratory variables, radiological features, treatment approach, and complications were retrospectively collected in two centers of Hubei province, China. Cox regression analysis was conducted to identify the risk factors for mortality. RESULTS: A total of 432 patients were enrolled, and the median patient age was 54 years. The overall mortality rate was 5.09% (22/432). As compared with the survivor group (n = 410), those in the non-survivor group (n = 22) were older, and they had a higher frequency of comorbidities and were more prone to suffer from dyspnea. Several abnormal laboratory variables indicated that acute cardiac injury, hepatic damage, and acute renal insufficiency were detected in the non-survivor group. Non-surviving patients also had a high computed tomography (CT) score and higher rate of consolidation. The most common complication causing death was acute respiratory distress syndrome (ARDS) (18/22, 81.8%). Multivariate Cox regression analysis revealed that hemoglobin (Hb) <90 g/L (hazard ratio, 10.776; 95% confidence interval, 3.075-37.766; p<0.0001), creatine kinase (CK-MB) >8 U/L (9.155; 2.424-34.584; p = 0.001), lactate dehydrogenase (LDH) >245 U/L (5.963; 2.029-17.529; p = 0.001), procalcitonin (PCT) >0.5 ng/ml (7.080; 1.671-29.992; p = 0.008), and CT score >10 (39.503; 12.430-125.539; p<0.0001) were independent risk factors for the mortality of COVID-19. CONCLUSIONS: Low Hb, high LDH, PCT, and CT score on admission were the predictors for mortality and could assist clinicians in early identification of poor prognosis among COVID-19 patients.

Prognostic value of neutrophil-to-lymphocyte ratio, lactate dehydrogenase, D-dimer, and computed tomography score in patients with coronavirus disease 2019.

BACKGROUND: This study aimed to explore the significance of neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), D-dimer, and CT score in evaluating the severity and prognosis of coronavirus disease 2019 (COVID-19). METHODS: Patients with laboratory-confirmed COVID-19 were retrospectively enrolled. The baseline data, laboratory findings, chest computed tomography (CT) results evaluated by CT score on admission, and clinical outcomes were collected and compared. Logistic regression was used to assess the independent relationship between the baseline level of the four indicators (NLR, LDH, D-dimer, and CT score) and the severity of COVID-19. RESULTS: Among the 432 patients, 125 (28.94%) and 307 (71.06%) were placed in the severe and non-severe groups, respectively. As per the multivariate logistic regression, high levels of NLR and LDH were independent predictors of severe COVID-19 (OR=2.163; 95% CI=1.162-4.026; p=0.015 for NLR>3.82; OR=2.298; 95% CI=1.327-3.979; p=0.003 for LDH>246 U/L). Combined NLR>3.82 and LDH>246 U/L increased the sensitivity of diagnosis in patients with severe disease (NLR>3.82 [50.40%] vs. combined diagnosis [72.80%]; p=0.0007; LDH>246 [59.2%] vs. combined diagnosis [72.80%]; p<0.0001). CONCLUSIONS: High levels of serum NLR and LDH have potential value in the early identification of patients with severe COVID-19. Moreover, the combination of LDH and NLR can improve the sensitivity of diagnosis.

Differential expression of microRNAs in xenografted Lewis lung carcinomas subjected to intermittent hypoxia: a next-generation sequence analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cancer mortality, but the underlying mechanism remains poorly understood. MicroRNAs (miRNAs) are confirmed to be involved in tumorigenesis and tumor progression. However, whether miRNAs have any differential expressions in OSA population needs to be elucidated. The aim of this experimental study was to determine the alterations of various miRNAs in xenograft mice exposed to chronic intermittent hypoxia (IH) which is considered a hallmark of OSA. METHODS: Sequencing was applied to screen the miRNAs of tumor tissues in xenograft mice exposed to IH and normoxia (control, CTL), respectively. Most differentially expressed miRNAs were verified by the quantitative real-time polymerase chain reaction (qRT-PCR). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway were performed to reveal the functional enrichment of the target genes regulated by the miRNAs. RESULTS: A total of 485 miRNAs (259 novel miRNAs and 226 known miRNAs) were differentially expressed between the IH and CTL groups. 154 miRNAs were upregulated and 331 miRNAs were downregulated among them. The top 5 differentially expressed known (miR-767, miR-466f-5p, miR-5122, miR-124-3p and miR-590-3p) and novel (miR-140, miR-130, miR-301, miR-177 and miR-90) miRNAs were validated by qRT-PCR. MiR-767, miR-124-3p, miR-590-3p and all novel miRNAs were upregulated while miR-466f-5p and miR-5122 were downregulated in IH-induced xenograft mice. In addition, GO and KEGG pathway analysis demonstrated that the predicted target genes, which were regulated by differentially expressed miRNAs were markedly enriched in related biological processes and pathways, including biological processes, cell metabolic and biosynthetic processes and molecular functions. CONCLUSIONS: Several altered miRNAs were detected in xenograft mice exposed to IH. The differentially expressed miRNAs in IH indicates that these miRNAs might involve in the molecular mechanism of tumorigenesis and tumor progression in OSA. Further studies are required to determinate the exact intermediation of certain miRNAs between IH and tumor progression.