Impaired intestinal barrier in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is often associated with multisystem damage. The gut is a pivotal organ that initiates the pathophysiological processes of multisystem diseases. Intermittent hypoxia resulting from OSA may impair the intestinal barrier prior to the induction of systemic inflammation. We hypothesize that the intestinal barrier markers D-lactic acid (D-LA) and intestinal fatty acid-binding protein (I-FABP) levels would be higher in patients with OSA. METHODS: Consecutive snoring and nonsnoring adults were included in this study and were grouped based on their apnea-hypopnea index (AHI) scores: the control group (AHI < 5) and the OSA group (AHI ≥ 5). Plasma D-LA and I-FABP levels were measured using colorimetry and ELISA, respectively. Other parameters, such as fasting levels of lipids, routine blood tests, and glucose were also assessed. RESULTS: Of 76 participants, patients in the OSA group accounted for 73% (55/76). Plasma D-LA and I-FABP levels were significantly higher in patients with OSA [7.90 (7.42) (IQR) vs. 0.88 (2.79) (IQR) mmol/L, p < 0.001 and 1851.99 ± 754.23 (SD) vs. 1131.98 ± 383.38 pg/mL, p < 0.001, respectively]. Increased glucose, triglycerides (TGs), leukocytes, neutrophils, and monocytes but decreased high density lipoprotein (HDL) were also found in patients with OSA. It was also observed that the increase in D-LA and I-FABP exhibited the strongest positive association with AHI (r = 0.443, p < 0.001; r = 0.645, p < 0.001), followed by the lowest SaO2 (p ≤ 0.001), BMI (p ≤ 0.017), glucose (p ≤ 0.011), and TGs (p ≤ 0.025). Moreover, multivariate regression analysis showed that D-LA (B = 0.823, p < 0.001) and I-FABP (B = 0.002, p = 0.017) were independently associated with OSA. CONCLUSIONS: The systemic expression of D-LA and I-FABP is dramatically higher in OSA patients, suggesting that hypoxia resulting from OSA might have the capacity to impair the intestinal barrier prior to the induction of multisystem dysfunction.

Independent association of severity of obstructive sleep apnea with lipid metabolism of atherogenic index of plasma (AIP) and apoB/apoAI ratio.

BACKGROUND: Cardiovascular diseases (CVDs) are highly prevalent in obstructive sleep apnea (OSA), and dyslipidemia is an important factor. Atherogenic index of plasma (AIP, log[TG/HDL-C]) and apolipoproteinB to apolipoproteinAI ratio (apoB/apoAI ratio) are considered high quality predictors of cardiovascular risk. However, the associations between OSA severity and AIP and apoB/apoAI ratio remained unclear. METHODS: A retrospective study was performed in 284 patients. Subjects were assessed with polysomnography (PSG) test, and OSA severity was defined by AHI. Data collected included anthropometric measurements, medical history, sleep parameters, fasting plasma lipids, fasting blood glucose, and insulin. RESULTS: Participants were classified based on AHI into the following groups: control group (n = 28), mild group (n = 52), moderate group (n = 53), and severe group (n = 151). Triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), apoAI, AIP, apoB/apoAI ratio (low-density lipoprotein cholesterol), LDL-C/HDL-C ratio, and HDL-C/apoAI ratio showed statistical significance among AHI subgroups (P < 0.05). The Pearson correlation analysis revealed that AIP (r = 0.32, P < 0.001) and apoB/apoAI ratio (r = 0.24, P < 0.001) were positively related to AHI. By multivariate linear regression analysis, we found that AHI was independently related to AIP (ß = 0.24, P = 0.001), apoB/apoAI ratio (ß = 0.24, P<0.001). CONCLUSION: AHI was independently correlated with AIP and apoB/apoAI ratio in OSA. Our findings suggested that AIP and apoB/apoAI ratio increased with OSA severity, which might be partly responsible for the high risk of CVDs in OSA.

The association of hemocyte profile and obstructive sleep apnea.

BACKGROUND: The hemocyte profile is one of the most frequently requested clinical laboratory tests. However, the analysis of blood cell indexes of obstructive sleep apnea (OSA) patients in previous studies was not comprehensive. And, this study aimed to fully analyze the blood routine in OSA patients. METHODS: A retrospective study was conducted on 1087 male patients, who were admitted to the sleep center of Nanfang Hospital from May 2013 to February 2018. According to the apnea hypopnea index (AHI), patients were divided into four groups: control group (AHI < 5, n = 135), mild OSA (5 ≦ AHI < 15, n = 185), moderate OSA (15 ≦ AHI < 30, n = 171), and severe OSA (AHI ≧ 30, n = 596). Data collected included sleep parameters, complete blood routine, body mass index (BMI), age, and comorbidities. RESULTS: In our study, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, erythrocytes, hemoglobin, hematocrit, platelets, MPV, and PDW-SD were statistically significant among the four groups based on AHI (P < 0.05), but no significant differences were found in MCV, RDW-SD, N/L, and P/L ratio (P > 0.05). Neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, hematocrit, platelets, and MPV were significantly correlated with AHI. Moreover, multiple linear regression analysis demonstrated that hematocrit (ß = 73.254, P = 0.001), neutrophils (ß = 1.414, P = 0.012), and lymphocytes (ß = 4.228, P < 0.001) were independently associated with AHI. CONCLUSION: Neutrophils, lymphocytes, and hematocrit were independently associated with OSA severity. And combining these three blood cell indicators could contribute to the diagnosis of OSA.

Circulating C3 and glucose metabolism abnormalities in patients with OSAHS.

PURPOSE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common breathing disorder during sleep characterized by multiple disease roots, including disorders of complement and glycometabolism. And the main purpose of the present study is to make clear the effect of complement C3 on glucose metabolism abnormalities in patients with OSAHS. METHODS: This was a cross-sectional study. Two hundred six patients, mean age 44.58 ± 11.84 years and 26 female patients (26/206), had been suspected with OSAHS and underwent overnight polysomnography. The assessment of complement levels included complement 3 (C3), complement 4 (C4), and serum total complement (TC). The measured indicators of glucose metabolism were fasting blood glucose (FPG), fasting insulin (FINS), and 75 g oral glucose tolerance test-derived glucose. A multivariate linear regression was used to determine relevant factors with 2-h postprandial blood glucose (2hPG) and C3. RESULTS: The patients were classified according to apnea-hypopnea index (AHI) into four groups: simple snore (n = 21), mild OSAHS (n = 43), moderate OSAHS (n = 35), and severe OSAHS (n = 107). The level of C3 in the severe OSAHS was higher than other groups (simple snore: 1.16 ± 0.18 g/L VS 1.00 ± 0.18 g/L, p < 0.001; mild OSAHS: 1.16 ± 0.18 g/L VS 1.04 ± 0.17 g/L, p < 0.001; moderate OSAHS: 1.16 ± 0.18 g/L VS 1.06 ± 0.14 g/L, p = 0.003) and no-severe OSAHS group (1.16 ± 0.18 g/L VS 1.04 ± 0.16 g/L, p < 0.001). And C3 was associated with AHI, average pulse oxygen saturation (A-spo2), homeostasis model assessment-insulin resistance (HOMA-IR), 2hPG, age, sleep stage (I + II)/TST, and sleep stage (III)/TST, respectively. HOMA-IR was correlated to AHI after adjustment with age and BMI. OSAHS was an independent risk of C3 regardless of obesity and sleep parameters (p = 0.002). After adjustment with neck circumference (NC), BMI, AHI, sleep stage (I + II)/TST, and sleep stage (III)/TST,C3 level was associated with 2hPG (p < 0.001). CONCLUSIONS: A high level in C3 is correlated with the occurrence of OSAHS and C3 alterations in OSAHS patients seem to contribute to disorders of glucose metabolism. And targeting OSAHS to improve glucose metabolism and immune function could be useful.

MiR-204-5p/Six1 feedback loop promotes epithelial-mesenchymal transition in breast cancer.

Epithelial-mesenchymal transition (EMT) is a vital process in epithelial cancer invasion and metastasis. The induction of EMT by Six1 has been described as a common mode of cancer progression, which could promote breast cancer migration and invasion. In the study, we found that miR-204-5p could suppress the migration and invasion of breast cancer cell lines. Since overexpression of Six1 promote EMT, we identified a mechanism by which miR-204-5p inhibited the EMT by downregulating the Six1, which was mediated by a conserved miR-204-5p seed-matching sequence in the 3'-UTR of Six1 mRNA. We also identified that upregulation of Six1 could downregulate miR-204-5p expression, affecting the migration and invasion of breast cancer cell lines. In conclusion, the frequent upregulation of Six1 and/or downregulation of miR-204-5p in breast cancer may shift the equilibrium of these reciprocal regulations and lock breast cancer cells in the mesenchymal state.

[The impact of obstructive sleep apnea hypopnea syndrome on glucose metabolism].

OBJECTIVE: To study the influence of obstructive sleep apnea hypopnea syndrome (OSAHS) on glucose metabolism and comprehensively analyze its related factors. METHODS: A total of 180 snoring patients were recruited in Sleep Disorder Center of Nanfang Hospital of Southern Medical University between January 2010 to June 2011. There were 140 patients with OSAHS and 40 subjects without OSAHS. All patients underwent both a full polysomnography (PSG) and plasma glucose measure, including fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT). The FPG, 1-hour post-challenge glucose (1 hPG) and 2-hour post-challenge glucose (2 hPG) were respectively compared in patients with different apnea hypopnea index (AHI), the lowest saturation of pulse oximetry (SpO2) and sleep architecture. RESULTS: The incidence of glucose metabolism disorders was higher in patients with OSAHS than that of those without (diabetes: 21.4% vs 5.0%; prediabetes: 34.3% vs 25.0%). The FPG, 1 hPG and 2 hPG in patients with different AHI was significantly different respectively (all P < 0.01), so as in patients with different lowest oxygen saturation (all P < 0.01). Post-load glucose levels of patients with different AHI were still significantly different after adjustment for neck circumference (1 hPG: P = 0.004; 2 hPG: P = 0.048). FPG, 1 hPG and 2 hPG were associated with AHI (r = 0.167, 0.277, 0.196, all P < 0.05), mean SpO2(r = -0.154, -0.214, -0.182, all P < 0.05) and the lowest SpO2(r = -0.224, -0.231, -0.159, all P < 0.05); While FPG, 1 hPG and 2 hPG were not significantly associated with N1 + N2, N3 and rapid eye movement (REM) sleeps (all P > 0.05). CONCLUSIONS: The risk of glucose metabolism disorders increased with the severity of OSAHS. Compared with fasting glucose, post-load glucose was more affected by OSAHS independent of obesity. Compared with sleep architecture or sleep efficiency, glucose metabolism disorders seem to be associated with hypoxia caused by OSAHS.

Sleep medicine knowledge, attitudes, and practices among medical students in Guangzhou, China.

PURPOSE: This study aimed to describe the knowledge, attitudes, and practices of Chinese medical students towards sleep medicine. METHODS: The authors surveyed medical students at Southern Medical University in 2009. Students completed a questionnaire before and after attending a 3-h sleep disorders course. RESULTS: All 324 questionnaires were returned. Less than one half of the students were aware that restless legs syndrome, somniloquy, and teeth grinding are sleep disorders. Only a small percentage of students knew that sleep disorders are related to diabetes, anemia, hyperlipidemia, and attention deficit syndrome. After the 3-h sleep disorders course, the percentage of students who regarded snoring, restless legs syndrome, nightmares, and somniloquy as sleep disorders increased from 64.9 to 92.7 %, 40.8 to 64.4 %, 48.0 to 60.3 %, and 33.5 to 59.9 % (P < 0.001), respectively. Sleep problems were considered to be a significant issue by 93.8 % of the students. The students thought that people with sleep disorders should seek treatment. Of the students, 81.3 % were interested in sleep medicine. The students considered that it is necessary to set up specialized sleep medicine departments to manage sleep disorders. Of the students, 76.8 % thought they or their friends had sleep problems, and 44.8 % consulted physicians about sleep problems. Greater than two thirds of the students (67.1 %) did not have formal education about sleep medicine. Few students were aware of medical schools offering a course in sleep medicine. Most of the students liked learning in the form of elective courses, lectures, or online course. The students also realized that having sleep medicine knowledge is needed as a physician. CONCLUSIONS: Chinese medical students attached importance to sleep disorders, but knew little about sleep disorders. Knowledge of sleep medicine can be improved with a short training course.

PBX1-promoted SFRP4 transcription inhibits cell proliferation and epithelial-mesenchymal transition in endometrial carcinoma.

OBJECTIVE: To explore the effects and mechanisms of action of the PBX1/secreted frizzled-related protein 4 (SFRP4) axis in endometrial carcinoma (EC). METHODS: The expression of PBX1 and SFRP4 was analyzed using bioinformatics prediction, followed by validation in EC cells using quantitative reverse transcription-polymerase chain reaction and western blotting. After transduction with overexpression vectors for PBX1 and SFRP4, migration, proliferation, and invasion of EC cells were measured, accompanied by the detection of E-cadherin, Snail, N-cadherin, Vimentin, ß-catenin, GSK-3ß, and C-myc expression. The association between PBX1 and SFRP4 was validated using dual luciferase reporter gene and chromatin immunoprecipitation assays. RESULTS: PBX1 and SFRP4 were downregulated in EC cells. Overexpression of PBX1 or SFRP4 resulted in weakened cell proliferation, migration, and invasion, as well as decreased expression of Snail, N-cadherin, Vimentin, ß-catenin, GSK-3ß, and C-myc and increased expression of E-cadherin. PBX1 bound to the SFRP4 promoter and promoted its transcription. Knockdown of SFRP4 reversed the repression of overexpressed PBX1 in the malignant phenotypes and EMT of EC cells, and PBX1 repressed Wnt/ß-catenin pathway activation by upregulating SFRP4 transcription. CONCLUSION: PBX1 inhibited activation of the Wnt/ß-catenin pathway by promoting SFRP4 transcription, thereby suppressing malignant phenotypes in EC cells and the EMT process.

Obstructive sleep apnea is related to alterations in fecal microbiome and impaired intestinal barrier function.

Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect fecal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers-intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Plasma D-LA and I-FABP were significantly elevated in patients with OSA. The severity of OSA was related to differences in the structure and composition of the fecal microbiome. Enriched Fusobacterium, Megamonas, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the fecal microbiome, intestinal barrier biomarkers, and AHI. The study confirms that changes in the intestinal microbiota are associated with intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.

Role of thioredoxin in lung disease.

Thioredoxin system is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. It includes thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH. Trx plays an essential role in cell function by limiting oxidative stress directly via antioxidant effects and indirectly by proteins interaction with key signal transduction molecules. A variety of signaling molecules have been implicated in the cytoprotection conferred by Trx, such as autophagic proteins, p38 mitogen-activated protein kinase, nuclear factor-κB, phosphatidylinositol 3-kinase. Recent studies indicated that Trx may contribute to the pathogenesis of COPD, asthma and lung injury. Enhanced Trx expression or application of recombinant Trx afforded protection in preclinical models of pulmonary tissue injury, which suggested Trx may be used in future therapeutic applications. The focus of this review is on the significance of Trx in various pulmonary diseases, which as a potential therapeutic strategy to protect against oxidative stress and inflammation.

Effect of automatic versus fixed continuous positive airway pressure for the treatment of obstructive sleep apnea: an up-to-date meta-analysis.

PURPOSE: This study was made to evaluate the effect of automatic continuous positive airway pressure (auto-CPAP) versus fixed continuous positive airway pressure (fixed CPAP) in reducing the apnea-hypopnea index (AHI) and the mean therapy pressure, improving subjective sleepiness, sleep architecture, patient compliance, and preference in patients with obstructive sleep apnea. METHODS: We searched the electronic databases MEDLINE, EMBASE, the Cochrane Library, and Google Scholar. Randomized controlled trials comparing auto-CPAP with fixed CPAP were reviewed. Continuous variables were presented as mean difference (MD), and dichotomous data as odds ratio (OR), both with 95% confidence intervals (CI). RESULTS: We identified 19 studies consisting of 845 patients. Compared to fixed CPAP, the use of auto-CPAP reduced mean therapy pressure (MD -1.64; 95% CI -2.46 to -0.82), improved patient compliance (MD 0.23; 95% CI 0.06 to 0.39), increased the percentage of total sleep time (TST) in slow wave sleep (MD 5.11; 95% CI 1.34 to 8.88), and decreased the percentage of TST in stage 2 sleep (MD -4.75; 95% CI -9.38 to -0.11). Moreover, more patients preferred auto-CPAP therapy (OR 3.65; 95% CI 1.27 to 10.53). There were nonsignificant trends towards better outcomes with auto-CPAP for AHI and Epworth Sleepiness Scale (MD -0.43; 95% CI -1.10 to 0.23, and MD -0.24; 95% CI -0.74 to 0.25, respectively), though these are of questionable clinical significance. CONCLUSIONS: There are some aspects of clinical care, such as a mild improvement in compliance, patient preference, and sleep architecture that appear to favor the use of auto-CPAP compared to fixed CPAP. The clinical relevance of these findings requires further study.

Predictive performances of 6 data mining techniques for obstructive sleep apnea-hypopnea syndrome.

PURPOSE: This study compared the effects of 6 types of obstructive sleep apnea-hypopnea syndrome (OSAHS) prediction models to develop a reference for selecting OSAHS data mining tools in clinical practice. METHODS: This cross-sectional study included 401 cases. They were randomly divided into 2 groups: training (70%) and testing (30%). Logistic regression, a Bayesian network, an artificial neural network, a support vector learning machine, C5.0, and a classification and regression tree were each adopted to establish 6 prediction models. After training, the 6 models were used to test the remaining samples and calculate the correct and error rates of each model. RESULTS: Twenty-one input variables for which the difference between the patient and nonpatient groups was statistically significant were considered. The models found the abdominal circumference, neck circumference, and nocturia ≥2 per night to be the most important variables. The support vector machine, neural network, and C5.0 models performed better than the classification and regression tree, Bayesian network, and logistic regression models. CONCLUSIONS: In terms of predicting the risk of OSAHS, the support vector machine, neural network, and C5.0 were superior to the classification and regression tree, Bayesian network, and logistic regression models. However, such results were obtained based on the data of a single center, so they need to be further validated by other institutions.

Screening of plasma exosomal lncRNAs to identify potential biomarkers for obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is highly prevalent, but frequently undiagnosed. The existing biomarkers of OSA are relatively insensitive and inaccurate. Long non-coding RNAs (lncRNAs) have no protein-coding ability but have a role in regulating gene expression. They are stably expressed in exosomes, easily and rapidly measurable. Changes in expression of exosomal lncRNAs can be useful for disease diagnoses. However, there are few reports on the association of exosomal lncRNAs with OSA. We aimed to investigate the exosomal lncRNA profiles to establish the differences between non-OSA, OSA with or without hypertension (HTN) and serve as a potential diagnostic biomarker. Methods: This diagnostic test included 63 participants: [normal control (NC) =25], (OSA =23), and (HTN-OSA =15). Expression profiling of lncRNAs in isolated exosomes was performed through high-throughput sequencing in 9 participants. Subsequently, OSA/HTN-OSA related lncRNAs were selected for validation by droplet digital polymerase chain reaction (ddPCR), receiver operating characteristic (ROC) curves were used to determine the diagnostic value. The reliabilities of the screened gene were further validated in another independent cohort: (NC =10), (OSA mild =10), (OSA moderate =11), and (OSA severe =10), the correlation between clinical features and its expression was analyzed. The MiRanda software was used to predict the binding sites of interaction between microRNA (miRNA) and target genes regulated by screened lncRNA. Results: We identified the differentially expressed lncRNAs and mRNAs in plasma exosomes of the NC, OSA, HTN-OSA groups. Most pathways enriched in differentially expressed lncRNAs and mRNAs had previously been linked to OSA. Among them, ENST00000592016 enables discrimination between NC and OSA individuals [area under curve (AUC) =0.846, 95% confidence interval (CI): 0.72-0.97]. The severity of OSA was associated with changes in the ENST00000592016 expression. Furthermore, ENST00000592016 affected the PI3K-Akt, MAPK, and TNF pathways by regulating miRNA expressions. Conclusions: This is the first report about differential expression of lncRNA in OSA and HTN-OSA exosomes. ENST00000592016 enables discrimination between NC and OSA individuals. This work enabled characterization of OSA and provided the preliminary work for the study of biomarker of OSA.

Activation of aryl hydrocarbon receptor (AhR) in mesenchymal stem cells modulates macrophage polarization in asthma.

Macrophage polarization has been demonstrated to exert a vital role on asthma pathogenesis. Mesenchymal stem cells (MSC) have the capacity to modulate macrophage differentiation from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype. However, the impact of MSC-macrophage interactions on asthma development and underlying mechanisms responsible for this interaction remain largely unknown. The aim of this study was to investigate the role of AhR expressed on MSC in macrophage polarization in a cockroach extract (CRE)-induced asthma mouse model. The studies here revealed that MSC polarized macrophages from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype in this model. The mRNA levels of interleukin (IL)-6, IL-1ß, and NOS2 as M1 markers were significantly decreased while those of select M2 markers such as Arg-1, FIZZ1, and YM-1 were significantly enhanced. It was also observed that aryl hydrocarbon receptor (AhR) signaling was significantly increased during asthma pathogenesis as demonstrated by enhanced mRNA expression of AhR, CYP1a1, and CYP1b1. It was also seen that the elevated AhR signaling was able to attenuate the onset of asthma. Use of an AhR antagonist (CH223191) resulted in significant inhibition of the AhR signaling and increases in M2 marker expression, but led to elevation of expression of M1 markers in the CRE-induced asthma model. Taken together, the current study showed that MSC can modulate macrophage polarization, in part, via activation of AhR signaling during CRE-induced asthma.

[Changes of the sodium channel in alveolar type II cells in pulmonary water transport in rats with oleic acid-induced acute lung injury].

OBJECTIVE: To determine the capability of alveolar fluid clearance and the changes of sodium channel in alveolar type II cells (ATII) in oleic acid-induced acute lung injury. METHODS: Forty four male Sprague-Dawley (SD) rats were randomized into a control group and an acute lung injury (ALI) group, with 22 rats in each group. The ALI model was established by oleic acid. The ATII cells were acutely isolated and purified, and the ATII cellular ultrastructure was observed by transmission electron microscope. In each group, the mRNA expression of 3 epithelial sodium channel (ENaC) subunits in acute isolated ATII cells from 8 rats were detected by reverse transcription-polymerase chain reaction (RT-PCR), while the extravascular lung water (EVLW) content was quantified in 7 rats by gravimetric measurement, and the lung histopathological changes were studies in 7 rats. RESULTS: In the ALI group, Smith lung injury score (7.6 +/- 0.8) and EVLW (0.80 +/- 0.17) ml were significantly higher than those in the control group [Smith score: (1.1 +/- 0.2), t = -20.859, P < 0.01; EVLW: (0.52 +/- 0.10) ml, t = -3.851, P < 0.01]. The transmission electron microscopic observation showed that there were degeneration, apoptosis, and lamellar body vacuolar changes in the ATII cells from the ALI rats. RT-PCR demonstrated that the alpha-subunit of the ENaC mRNA expression was the highest among the 3 subunits (F = 4.40, P = 0.02). In the ALI group, mRNA expressions of all the 3 ENaC subunits in acutely isolated ATII cells were decreased as compared to those in the control group [alpha-subunit: (51 +/- 9)% vs (82 +/- 7)%, t = 7.61, P < 0.01; beta-subunit: (13 +/- 7)% vs (25 +/- 4)%, t = 4.53, P < 0.01; gamma-subunit: (31 +/- 15)% vs (40 +/- 17)%, t = 3.01, P < 0.05; respectively]. CONCLUSIONS: The capacity of alveolar fluid clearance was attenuated in oleic acid-induced acute lung injury. The ENaC subunit mRNA levels of ATII cells were significantly decreased in ALI rats.

Independent association of vitamin D and insulin resistance in obstructive sleep apnea.

BACKGROUND: Vitamin D insufficiency and/or high levels of parathyroid hormone (PTH) seem to be associated with abnormal glucose metabolism, which is frequent in obstructive sleep apnea (OSA). The purpose of this study was to investigate vitamin D and PTH concentrations in OSA, and to explore potential links between vitamin D, PTH and insulin resistance (IR). METHODS: A total of 112 subjects with suspected OSA were recruited consecutively, and evaluated by polysomnography (PSG) to determine the number of apnea and hypopnea episodes per hour of sleep (apnea/hypopnea index: AHI). OSA was diagnosed for AHI≥5. Average (APO2) and minimum pulse oxygen saturation (MPO2) were assessed during PSG as indices of nocturnal hypoxemia. After overnight fasting, a standard 75g oral glucose tolerance test was performed. Serum 25-hydroxyvitamin D, PTH, fasting glucose and fasting insulin were also measured. Homeostasis model assessment (HOMA) was used to evaluate IR: HOMA-IR=fasting plasma insulin×fasting plasma glucose/22.5, with "insulin resistance" defined as HOMA-IR>2.7. RESULTS: Patients were classified into 4 groups according to AHI: control group (AHI<5, n=8), mild OSA (5≤AHI<15, n=18), moderate OSA (15≤AHI<30, n=33), and severe OSA (AHI≥30, n=53). They were also classified, according to HOMA-IR, as insulin-resistant (HOMA-IR>2.7, n=59) or non-insulin-resistant (HOMA-IR≤2.7, n=45). There were no significant differences in vitamin D or PTH levels between AHI groups. HOMA-IR was significantly higher in severe OSA than in controls (P=0.019). Vitamin D concentration correlated negatively with AHI (r=-0.242, P=0.01) and with HOMA-IR (r=-0.338, P<0.001). PTH concentration correlated negatively with vitamin D concentration (P<0.001), but not with AHI or HOMA-IR. HOMA-IR correlated positively with AHI (r=0.368, P<0.001) and negatively with MPO2 (r=-0.414, P<0.001). Finally, stepwise linear multivariate regression showed that vitamin D concentration (ß=-0.209, P=0.014) and MPO2 (ß=-0.221, P=0.011) were independently associated with HOMA-IR. CONCLUSION: Subjects with severe OSA may have a low vitamin D level associated with increased risk of IR. Vitamin D was independently associated with IR in OSA. Vitamin D insufficiency may play a role in the pathogenesis of IR in OSA.

Beneficial response of blood pressure to short-term continuous positive airway pressure in Chinese patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is common in people with hypertension and cardiac rhythm disorder. The objectives of this study were to determine the effect of short-term continuous positive airway pressure (CPAP) on blood pressure (BP) and cardiac rhythm in Chinese patients with moderate to severe OSAHS. PATIENTS AND METHODS: Eligible patients in the two hospitals were consecutively enrolled into the prospective study. Ambulatory BP monitoring and Holter monitoring were both performed for 24 h in 214 patients who previously encountered a full night polysomnography. Ambulatory BP was measured again in the follow-up of 59 patients with OSAHS who underwent home CPAP for 30 days, whereas Holter was repeated within 2-3 days after institution of CPAP therapy in 15 patients with OSAHS. RESULTS: Fifty-one patients with OSAHS with hypertension who used CPAP for at least 4 h/night received 30 days of CPAP treatment. Added CPAP on usual antihypertension treatment showed that systolic BP, diastolic BP, and mean arterial BP were significantly reduced at night (5.08, 3.05, and 3.73 mmHg, respectively), in the morning (6.31, 4.83, and 5.32 mmHg, respectively), and during the whole a day (3.09, 2.60, and 2.76 mmHg, respectively). There were no significant changes in daytime BP values but did reduce daytime BP by 2.09, 2.37, and 2.28 mmHg, respectively. In addition, CPAP therapy resulted in abolition of most sinus pauses and atrioventricular block in the 15 patients with OSAHS having coexisting pathologically rhythm disturbances, whereas the effect on other types of arrhythmia was not effective enough. CONCLUSION: Short-term CPAP reduced BP modestly in patients with OSAHS with hypertension, especially in the morning and at night-time.

Alterations of IGF-1, complement C3 and superoxide dismutase in patients with moderate-to-severe obstructive sleep apnea hypopnea syndrome.

AIM: To evaluate various biomarkers of metabolism, immunity and inflammation in obstructive sleep apnea hypopnea syndrome (OSAHS). MATERIALS & METHODS: After overnight polysomnography, blood was collected from 292 OSAHS patients or healthy volunteers. Serum content of inflammatory, immune, metabolic biomarkers were investigated. In addition, the effects of 1-month continuous positive airway pressure (CPAP) were studied in moderate/severe OSAHS. RESULTS: C3, serum total complement activity, superoxide dismutase, uric acid were significantly higher in moderate/severe OSAHS than that in no/mild OSAHS. In contrast, IGF-1 in moderate/severe OSAHS was lower than it in no/mild OSAHS, which was negative correlated with apnea-hypopnea index. Moreover, CPAP significantly decreased C3, meanwhile elevated IGF-1. CONCLUSION: C3, serum total complement activity and superoxide dismutase were higher in moderate/severe OSAHS, while IGF-1 decreased. Elevated C3 and reduced IGF-1 in moderate/severe OSAHS may be reversed by CPAP.

[Alterations of respiratory resistance in patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To evaluate the association between the components of airway resistance and severity of obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 234 patients with snoring during sleep underwent full-night polysomnography in our center between January, 2015 and September, 2017. According to the apnea-hypopnea index (AHI) scores, the patients were divided into non-OSAHS group (AHI scores <5), mild or moderate OSAHS group (5-30) group, and severe OSAHS group (>30). The pulmonary function and respiratory resistance of the patients were assessed using spirometry and impulse oscillometry, respectively, and the correlation between the parameters of respiratory resistance and the severity of AHI were analyzed. RESULTS: The non-OSAHS, mild or moderate OSAHS, and severe OSAHS groups consisted of 31, 90 and 113 patients, respectively. The patients with severe OSAHS had significantly higher levels of respiratory resistance at 5 Hz (R5) and 20 Hz (R20), FEF50% and MMEF than those in the other two groups (P<0.05). Bivariate correlation analysis identified positive correlations of R5 (r=0.259, P=0.000), R20 (r=0.298, P=0.000) and FEF50% (r=0.176, P=0.007) with AHI scores of the patients. CONCLUSION: Patients with OSAHS have increased respiratory resistance in the large airways and compensatory reduction in small airway resistance.

Functional analysis of CD14+HLA-DR-/low myeloid-derived suppressor cells in patients with lung squamous cell carcinoma.

Immunomodulatory therapy is a potential effective treatment for advanced cancer that may provide an alternative to chemotherapy, which patients can experience adverse side effects to. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to cause T-cell tolerance in rodents and humans; however, little is known about the role of MDSCs in squamous cell carcinoma. In the present study, the role of MDSCs in lung squamous cell carcinoma was investigated. Peripheral blood from 78 patients with lung squamous cell carcinoma and 30 healthy controls was examined for the presence and function of human MDSCs, denoted as monocyte differentiation antigen CD14-positive HLA class II histocompatibility antigen DR-negative/low (CD14+ HLA-DR-/low) cells by flow cytometry. The sorted T-cell surface glyoprotein CD3 (CD3)+ cells and CD14+HLA-DR-/low cells were subsequently co-cultured with a tumor cell line (NCI-H226). T-cell apoptosis was detected using annexin-V-fluorescein isothicyanate and 7-aminoactinomycin D. Interferon-γ (IFN-γ) levels were detected using an ELISA. The frequency of MDSCs in the peripheral blood mononuclear cells (PBMCs) from patients with lung squamous cell carcinoma was significantly higher compared with that of the healthy controls (P<0.05), whereas the frequency of T-cell surface glyoprotein CD4 (CD4)+ T cells and CD8+ T cells in PBMCs was significantly decreased (P<0.05). In an MDSC/CD8+ co-culture system, the proportion of CD8+ T-cell apoptosis significantly increased with the increase in ratio of MDSCs (P<0.05), while the proportion of tumor cell apoptosis significantly decreased (P<0.05). The concentration of IFN-γ significantly decreased with the increase in MDSCs (P<0.05). Therefore, MDSCs participate in the immune escape of lung squamous cell carcinoma, and may provide a possible therapeutic strategy for the treatment of this disease.