TMEM132A regulates mouse hindgut morphogenesis and caudal development.

Caudal developmental defects, including caudal regression, caudal dysgenesis and sirenomelia, are devastating conditions affecting the skeletal, nervous, digestive, reproductive and excretory systems. Defects in mesodermal migration and blood supply to the caudal region have been identified as possible causes of caudal developmental defects, but neither satisfactorily explains the structural malformations in all three germ layers. Here, we describe caudal developmental defects in transmembrane protein 132a (Tmem132a) mutant mice, including skeletal, posterior neural tube closure, genitourinary tract and hindgut defects. We show that, in Tmem132a mutant embryos, visceral endoderm fails to be excluded from the medial region of early hindgut, leading directly to the loss or malformation of cloaca-derived genitourinary and gastrointestinal structures, and indirectly to the neural tube and kidney/ureter defects. We find that TMEM132A mediates intercellular interaction, and physically interacts with planar cell polarity (PCP) regulators CELSR1 and FZD6. Genetically, Tmem132a regulates neural tube closure synergistically with another PCP regulator Vangl2. In summary, we have identified Tmem132a as a new regulator of PCP, and hindgut malformation as the underlying cause of developmental defects in multiple caudal structures.

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This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study.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.

The loss of Hh responsiveness by a non-ciliary Gli2 variant.

Hedgehog signaling is crucial for vertebrate development and physiology. Gli2, the primary effector of Hedgehog signaling, localizes to the tip of the primary cilium, but the importance of its ciliary localization remains unclear. We address the roles of Gli2 ciliary localization by replacing endogenous Gli2 with Gli2(ΔCLR), a Gli2 variant not localizing to the cilium. The resulting Gli2(ΔCLRKI) and Gli2(ΔCLRKI);Gli3 double mutants resemble Gli2-null and Gli2;Gli3 double mutants, respectively, suggesting the lack of Gli2(ΔCLR) activation in development. Significantly, Gli2(ΔCLR) cannot be activated either by pharmacochemical activation of Smo in vitro or by loss of Ptch1 in vivo. Finally, Gli2(ΔCLR) exhibits strong transcriptional activator activity in the absence of Sufu, suggesting that the lack of its activation in vivo results from a specific failure in relieving the inhibitory function of Sufu. Our results provide strong evidence that the ciliary localization of Gli2 is crucial for cilium-dependent activation of Hedgehog signaling.

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.

C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals.

The primary cilium plays critical roles in vertebrate development and physiology, but the mechanisms underlying its biogenesis remain poorly understood. We investigated the molecular function of C2 calcium-dependent domain containing 3 (C2cd3), an essential regulator of primary cilium biogenesis. We show that C2cd3 is localized to the centriolar satellites in a microtubule- and Pcm1-dependent manner; however, C2cd3 is dispensable for centriolar satellite integrity. C2cd3 is also localized to the distal ends of both mother and daughter centrioles and is required for the recruitment of five centriolar distal appendage proteins: Sclt1, Ccdc41, Cep89, Fbf1, and Cep164. Furthermore, loss of C2cd3 results in failure in the recruitment of Ttbk2 to the ciliary basal body as well as the removal of Cp110 from the ciliary basal body, two critical steps in initiating ciliogenesis. C2cd3 is also required for recruiting the intraflagellar transport proteins Ift88 and Ift52 to the mother centriole. Consistent with a role in distal appendage assembly, C2cd3 is essential for ciliary vesicle docking to the mother centriole. Our results suggest that C2cd3 regulates cilium biogenesis by promoting the assembly of centriolar distal appendages critical for docking ciliary vesicles and recruiting other essential ciliogenic proteins.

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.

Dual function of suppressor of fused in Hh pathway activation and mouse spinal cord patterning.

The morphogen Sonic hedgehog, one of the Hedgehog (Hh) family of secreted proteins, plays a key role in patterning the mammalian spinal cord along its dorsoventral (D/V) axis through the activation of Glioma-associated oncogene (Gli) family of transcription factors. Suppressor of Fused (Sufu), a Gli-interacting protein, modulates the D/V patterning of the spinal cord by antagonizing Hh signaling. The molecular mechanisms underlying the function of Sufu in Hh pathway activation and spinal cord D/V patterning remain controversial, particularly in light of recent findings that Sufu protects Gli2 and Gli3 proteins from proteasomal degradation. In the current study, we show that Hh pathway activation and dorsal expansion of ventral spinal cord cell types in the absence of Sufu depend on the activator activities of all three Gli family proteins. We also show that Sufu plays a positive role in the maximal activation of Hh signaling that defines the ventral-most cell fate in the mammalian spinal cord, likely through protecting Gli2 and Gli3 proteins from degradation. Finally, by altering the level of Gli3 repressor on a background of reduced Gli activator activities, we reveal an important contribution of Gli3 repressor activity to the Hh pathway activation and the D/V patterning of the spinal cord.

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∘).

Changes of blood gas analysis in moderate-to-severe acute respiratory distress syndrome patients during long-term prone position ventilation: a retrospective cohort study.

Background: Prone position ventilation (PPV) has been recommended for patients with acute respiratory distress syndrome (ARDS) to improve oxygenation. However, whether prolonged prone ventilation will aggravate hyperoxia and whether abdominal compression will aggravate permissive hypercapnia acidosis are topics of concern. We carried out a retrospective analysis to investigate the issues above. Methods: Clinical data were collected from 97 moderate-to-severe ARDS patients who received PPV as part of their treatment in the intensive care unit (ICU) of the First Affiliated Hospital of Guangzhou Medical University from November 2015 to May 2021. We collected arterial blood gas of patients according to the 3 periods: supine position ventilation (SPV), PPV early stage (within 4 hours), and PPV middle and late stage (6 hours or later). We established a linear mixed-effects models with "body position changes, times of PPV, gender, age, baseline SOFA, and baseline APACHE II" as fixed effects, and individual and the number of prone positions as random intercept and random slope to investigate the effect of body position changes on blood gas analysis. Results: Among the 97 patients received PPV included, 51 were ICU survivors. Arterial partial pressure of oxygen (PaO2) and PaO2/fraction of inspired oxygen (FiO2) ratio were significantly higher at the early, middle and late stages of PPV than those in SPV [PFR (mmHg): 158 (118.00, 203.00) vs. 161 (129.00, 202.75) vs. 123 (91.75, 163.00), P<0.05]. Despite the synchronized reduction of FiO2, the incidence of hyperoxia in the prone position was still significantly higher than that in the supine position [hyperoxia (%):33.33 vs. 33.56 vs. 12.42, P<0.05]; there was no significant change in arterial carbon dioxide partial pressure (PaCO2) at each stage of PPV, but there was a significant increase in PH at PPV middle and late stages than those at early stage [PH: 7.39 (7.34, 7.42) vs. 7.37 (7.31, 7.41), P<0.05]. Conclusions: Although PPV improves the patients' oxygenation, the associated incidence of hyperoxia exceeds 33%. Down-regulate FiO2 more sharply after PPV is necessary, if oxygenation conditions permit. PPV may alleviate the acidosis associated with permissive hypercapnia in ARDS patients treated with lung protective ventilation strategy (LPVS).

The co-mutation of EGFR and tumor-related genes leads to a worse prognosis and a higher level of tumor mutational burden in Chinese non-small cell lung cancer patients.

BACKGROUND: Lung cancer is the leading cause of cancer mortality in China. The clinicopathologic features and genetic profile of Chinese lung cancer patients need to be investigated. This study evaluated the gene mutation profile, analyzed the frequency of concurrent genes in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients, and determined its prognostic value. METHODS: We collected the clinical data from 151 initially diagnosed patients NSCLC. Tumor samples underwent targeted next-generation sequencing (NGS). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. RESULTS: Among the 151 participants, the mutational profile revealed alterations in 29 genes, where TP53 (37.09%) and EGFR (30.46%) exhibited the highest mutation rates. Mutations in the EGFR gene were most prevalent (40%) in adenocarcinoma (LUAD) and were only present in 8.8% of participants with squamous cell carcinoma (LUSC). The most frequently mutated genes in LUAD patients were TP53 (47%), followed by KRAS (11.7%). In all 39 participants with EGFR mutations, TP53, KRAS, PIK3CA, APC, and FBXW7 were also mutated. Those with only EGFR mutation appeared to have a better prognosis; however, the difference was not statistically significant. Tumor mutational burden (TMB) was roughly significantly increased in patients who harbored EGFR and other mutant driver genes, compared with only EGFR mutant patients. The TMB value was significantly higher in those with P53 mutation than in P53 wild-type patients. CONCLUSIONS: We described the genetic profiles of NSCLC and compared the difference in genetic profiles between LUAD and LUSC. The concomitant genetic alterations might be a poor prognostic factor for patients with EGFR mutation, and TMB might be prognostically related to the co-mutations of EGFR and other genes.

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.

Effect of IFN-α and other commonly used nebulization drugs in different nebulization methods on the resistance of breathing circuit filters under invasive mechanical ventilation.

Background: Interferon (IFN) is widely used in clinical practice and nebulization inhalation is one of the commonly used routes of administration. However, nebulization drugs such as interferon-α (IFN-α) with large molecular weights may deposit in the membrane of the breathing filters, causing its resistance to gradually increase. Thus, our study explores the effect of IFN-α and other nebulization drugs on the resistance of breathing circuit filters under invasive mechanical ventilation. Methods: We divided 96 breathing filters into eight groups. The baseline group was not treated while the blank group was installed but were not nebulized. The remaining groups received jet nebulized or vibrating nebulized with either normal saline, Combivent, Amphotericin B, or IFN-α at a frequency of once every 12 hours separately and were removed from the breathing circuit after 24 hours. The resistance of the filter of each group was then measured and statistical comparisons were made. Results: Filter resistance of the IFN-α jet nebulization group was greater than that of the other groups, and there were statistical differences except for the Amphotericin B jet nebulization group. Comparison of the resistance [cmH2O/(L·s)] of the IFN-α jet nebulization group vs. the baseline group showed 2.56 (2.40, 2.68) vs. 2.26 (2.03, 2.40), P=0.037; of the IFN-α jet nebulization group vs. the blank group showed 2.56 (2.40, 2.68) vs. 2.11 (1.98, 2.27), P=0.003; of the IFN-α jet nebulization group vs. the normal saline group: 2.56 (2.40, 2.68) vs. 2.16 (2.08, 2.32), P=0.023; of the IFN-α jet nebulization group vs. the Combivent jet nebulization group: 2.56 (2.40, 2.68) vs. 2.18 (2.14, 2.27), P=0.018; and of the IFN-α jet nebulization group vs. the Amphotericin B jet nebulization group: 2.56 (2.40, 2.68) vs. 2.33 (2.05, 2.45), P=0.221. The effect of jet nebulization and vibrating mesh nebulization on the resistance of breathing filters showed no significant statistical difference. Conclusions: Jet nebulization with IFN-α significantly increased the resistance of the breathing filter within 24 hours and there was no significant difference in filter resistance between jet nebulization and vibrating mesh nebulization of IFN-α or Amphotericin B.