Blood urea nitrogen and clinical prognosis in patients with COVID-19: A retrospective study.

The aim of this study was to estimate the association between blood urea nitrogen (BUN) and clinical prognosis in patients with COVID-19. A multicenter, retrospective study was conducted in adult patients with COVID-19 in 3 hospitals in Zhenjiang from January 2023 to May 2023. Patients were divided into survival and death group based on whether they survived at day 28. The demographic, comorbidities, and laboratory data were independently collected and analyzed, as well as clinical outcomes. Total 141 patients were enrolled and 23 (16.3%) died within 28 days. Patients who died within 28 days had a higher level of BUN compared with survivors. Bivariate logistic regression analysis showed that BUN was a risk factor for 28-day mortality in patients with COVID-19. ROC curve showed that BUN could predict 28-day mortality of COVID-19 patients (AUC = 0.796, 95%CI: 0.654-0.938, P < .001). When the cutoff value of BUN was 7.37 mmol/L, the sensitivity and specificity were 84.62% and 70.31%. Subgroup analysis demonstrated that hyper-BUN (≥7.37 mmol/L) was associated with increased 28-day mortality among COVID-19 patients. Patients with COVID-19 who died within 28 days had a higher level of BUN, and hyper-BUN (≥7.37 mmol/L) was associated with increased 28-day mortality.

Clinical significance of serum IgM and IgG levels in COVID-19 patients in Hubei Province, China.

Background: There have been many studies about coronavirus disease 2019 (COVID-19), but the clinical significance of quantitative serum severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific IgM and IgG levels of COVID-19 patients have not been exhaustively analyzed. We aimed to investigate the time profiles of these IgM/IgG levels in COVID-19 patients and their correlations with clinical features. Methods: A multicenter clinical study was conducted from February 20 to March 5 2020. It involved 179 COVID-19 patients (108 males and 71 females) from five hospitals in Huangshi in Hubei Province, China. To detect SARS-CoV-2-specific IgM/IgG, quantitative antibody assays (two-step indirect immunoassays with direct chemiluminescence technology) based on the nucleocapsid protein (NP) and spike protein 1 (S1) were used. For normally distributed data, means were compared using the t-test, χ 2-test, or exact probability method. For categorical data, medians were compared using Mann-Whitney U test. Results: The median age was 57 (44-69) years (58 [38-69] for males and 57 [49-68] for females). The median duration of positive nucleic acid test was 22.32 (17.34-27.43) days. The mortality rate was relatively low (3/179, 1.68%). Serum SARS-CoV-2-specific IgG was detected around week 1 after illness onset, gradually increased until peaking in weeks 4 and 5, and then declined. Serum IgM peaked in weeks 2 and 3, then gradually declined and returned to its normal range by week 7 in all patients. Notably, children had milder respiratory symptoms with lower SARS-CoV-2-specific IgM/IgG levels. The duration of positive nucleic acid test in the chronic obstructive pulmonary disease (COPD) group was 30.36 (18.99-34.76) days, which was significantly longer than that in the non-COPD group (21.52 [16.75-26.51] days; P = 0.025). The peak serum SARS-CoV-2-specific IgG was significantly positively correlated with the duration of positive nucleic acid test. The incidence rate of severe and critical cases in the IgMhi group (using the median IgM level of 29.95 AU/mL as the cutoff for grouping) was about 38.0% (19/50), which was twice as much as that in the IgMlo group (18.4%; 9/49). The patients with positive chest imaging and lymphocytopenia (<1 × 109/L) had a higher SARS-CoV-2-specific IgM level. Conclusions: Quantitative SARS-CoV-2-specific IgM and IgG levels are helpful for the diagnosis, severity classification, and management of COVID-19 patients, and they should be monitored in each stage of this disease.

The role of mitophagy in the mechanism of genioglossal dysfunction caused by chronic intermittent hypoxia and the protective effect of adiponectin.

PURPOSE: Dysfunction of the genioglossus muscle is important in the pathogenesis of obstructive sleep apnea due to chronic intermittent hypoxia (CIH). Mitochondrial impairment resulting from hypoxia is mitigated by mitophagy to avoid cell apoptosis in cardiomyocytes. This project was designed to explore the effects of CIH on mitophagy in the genioglossus muscle and the impact of adiponectin (Ad). METHODS: One hundred eighty male SD rats were randomly divided into 3 groups (normal control [NC], CIH, and CIH + Ad groups), with 60 rats in each group observed for 5 weeks. Comparisons of serum Ad levels, mitochondrial structure and function, mitophagy, and cell apoptosis in the genioglossus were made at different time points. RESULTS: (1) The CIH group was significantly different from the NC group as follows: During the first 3 weeks, serum Ad levels, the reactive oxygen species (ROS), relative proteins and mRNA of mitophagy, autophagy biomarker LC3-II, and autophagosomes increased, while during the last 2 weeks, most parameters decreased. (2) There was no difference among the 3 groups in mitochondrial structure and function-associated mRNA during the first 3 weeks, while damaged mitochondrial structures were growing during the last 2 weeks. Exacerbation of apoptosis was also detected in the last 2 weeks. (3) All of the damage was partially alleviated in the CIH + Ad group in contrast to CIH group at the end of this study. CONCLUSION: Disturbances of genioglossal mitophagy could be related to damaged mitochondrial structure and function induced by CIH, which could be alleviated by supplementation of exogenous Ad via increasing mitophagy.

miR-1260b Activates Wnt Signaling by Targeting Secreted Frizzled-Related Protein 1 to Regulate Taxane Resistance in Lung Adenocarcinoma.

Objectives: MicroRNAs (miRNAs) have been demonstrated to contribute to carcinogenesis; however, their association with tumor chemoresistance is not fully understood. In this study we aimed to investigate the molecular mechanisms involved in resistance to taxane-based chemotherapy in lung adenocarcinoma (LAD). Methods: We established paclitaxel-resistant A549 cells (A549/PTX) and docetaxel-resistant H1299 cells (H1299/DTX). In order to hit the mark, we employed multiple methods including qRT-PCR, western blotting analysis, loss/gain-of-function analysis, luciferase assays, drug sensitivity assays, animal experiment, wound-healing assay, and invasion assay. Results: Bioinformatics analysis and a luciferase reporter assay revealed that secreted frizzled-related protein 1 (SFRP1) is a direct target of miR-1260b. By qRT-PCR analysis, we found that miR-1260b was significantly upregulated in taxane-resistant cells as compared to parental cells. Suppression of miR-1260b reversed the chemoresistance of human LAD cells to taxanes both in vitro and in vivo, whereas ectopic miR-1260b expression decreased the sensitivity of parental LAD cell lines to taxanes. Downregulation of miR-1260b expression inactivated the Wnt signaling pathway and reversed the epithelial-mesenchymal transition (EMT) phenotype of taxane-resistant LAD cells. In clinical tumor tissue samples, high miR-1260b expression was detected in tumors of non-responding patients treated with taxane-based chemotherapy and was associated with low SFRP1 expression and poor prognosis. Conclusions: Our findings reveal that targeting of the miR-1260b/SFRP1/Wnt signaling axis might provide a novel strategy for overcoming chemotherapy resistance in LAD.

Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are being wildly used as target therapy in non-small-cell lung cancer (NSCLC). However, NSCLC patients with wild-type EGFR and KRAS mutation are primary resistant to EGFR-TKIs such as gefitinib. Curcumin has been known as a potential therapeutic agent for several major human cancers. In this study, we investigated the effect of curcumin on the reversal of gefitinib resistance in NSCLC cells as well as their molecular bases. METHODS: H157 (wild-type EGFR and KARS mutation) and H1299 (wild-type EGFR and HRAS mutation) cells were treated with gefitinib or curcumin alone, or the two combination, and then cell viability, EGFR activity, expressions of Sp1 and Sp1-dependent proteins and receptor tyrosine kinases, markers of autophagy and apoptosis were examined by using CCK-8, colony formation, immunoblot, quantitative PCR, immunofluoscence, and flow cytometry assays. Also xenograft experiments were conduced to test the synergism of curcumin to gefitinib. RESULTS: Our results showed that curcumin significantly enhanced inhibitory effect of gefitinib on primary gefitinib-resistant NSCLC cell lines H157 and H1299. Combination treatment with curcumin and gefitinib markedly downregulated EGFR activity through suppressing Sp1 and blocking interaction of Sp1 and HADC1, and markedly suppressed receptor tyrosine kinases as well as ERK/MEK and AKT/S6K pathways in the resistant NSCLC cells. Meanwhile, combination treatment of curcumin and gefitinib caused dramatic autophagy induction, autophagic cell death and autophagy-mediated apoptosis, compared to curcumin or gefitinib treatment alone, as evidenced by the findings that curcumin and gefitinib combination treatment-produced synergistic growth inhibition and apoptosis activation can be reversed by pharmacological autophagy inhibitors (Baf A1 or 3-MA) or knockdown of Beclin-1 or ATG7, also can be partially returned by pan-caspase inhibitor (Z-VAD-FMK) in H157 and H1299 cells. Xenograft experiments in vivo yielded similar results. CONCLUSIONS: These data indicate that the synergism of curcumin on gefitinib was autophagy dependent. Curcumin can be used as a sensitizer to enhance the efficacy of EGFR-TKIs and overcome the EGFR-TKI resistance in NSCLC patients with wild-type EGFR and/or KRAS mutation.

Adiponectin protects the rats liver against chronic intermittent hypoxia induced injury through AMP-activated protein kinase pathway.

This study was performed to assess the effect of chronic intermittent hypoxia (CIH) on the liver, the associated mechanisms and the potential therapeutic roles of adiponectin (Ad). Sixty rats were randomly assigned to four groups: the normal control (NC), NC and Ad supplement (NC + Ad), CIH, and CIH and Ad supplement (CIH + Ad) groups. The rats in the CIH and CIH + Ad groups were exposed to a hypoxic environment for 4 months. Rats in the NC + Ad and CIH + Ad groups were also treated with an intravenous injection of Ad (10 ug), twice a week. The plasma levels of hepatic enzymes, serum triglyceride, liver triglyceride, fasting blood glucose and hepatic cell apoptosis in hepatic tissue, were higher in the CIH group than in the NC and NC + Ad groups. However, the Ad supplementation in the CIH + Ad group rescued the hepatic tissue insult by activating the AMP-activated protein kinase (AMPK) pathway. In conclusion, Ad could protect against CIH-induced hepatic injury partly through the AMPK pathway.

[Effects of chronic intermittent hypoxia on oxidative stress and inflammatory response and the interventional roles of adiponectin].

OBJECTIVE: To explore the effects of chronic intermittent hypoxia (CIH) on oxidative stress and inflammatory response and the interventional roles of adiponectin (Ad). METHODS: A total of 45 male Wistar rats were randomly divided into three groups of control group, CIH and CIH+Ad (n = 15 each). The control group breathed room air while the CIH and CIH+Ad groups received CIH 8 h/d for 5 successive weeks. The CIH+Ad group Ad had an injection of 10 µg once a week through tail vein. At the end of experiment (Day 35), comparison was performed among three groups about Ad, tumor necrosis factor α (TNF-α), C-reactive protein (CRP) and interleukin (IL) 6 from serum as well as malondialdehyde, superoxide dismutase (SOD), myeloperoxidase (MPO), reactive oxygen spieces (ROS) and nuclear factor (NF) κB from genioglossus. RESULTS: Serum Ad level in CIH group was lower than those in control and CIH+Ad groups ((4 208 ± 2 239) vs (7 051 ± 2 432) and (6 405 ± 2 384) ng/ml, all P < 0.05) with no statistic difference between control and CIH+Ad groups. Both serum levels of TNF-α and CRP were higher in CIH group than those in control and CIH+Ad groups ((70.87 ± 35.16) vs (26.54 ± 20.32) and (29.50 ± 22.54) pg/ml, as well as (31.84 ± 11.48) vs (22.68 ± 9.63), (25.32 ± 8.34) mg/L, all P < 0.05)with no significant difference between control and CIH+Ad groups. Serum IL-6 levels were all higher in CIH group and CIH+Ad group than that in control group ((30.54 ± 12.25) and (23.04 ± 13.) vs (14.10 ± 8.83) pg/ml, all P < 0.05) with no significant difference between CIH and CIH+Ad groups. Genioglossal malondialdehyde level was significantly elevated in CIH group than those in control and CIH+Ad groups ((8.05 ± 4.53) vs (5.18 ± 3.03) and ((5.74 ± 3.06) nmol/mg, all P < 0.01) with no significant difference between control and CIH+Ad groups. Genioglossal SOD activity was lower in CIH+Ad group than that in CIH group but higher than that in control group ((42.42 ± 23.17) vs (61.77 ± 36.38) and (18.62 ± 11.67) U/mg, all P < 0.05). Genioglossal MPO levels were significantly higher in both CIH and CIH+Ad groups than that in control group ((0.40 ± 0.29) and (0.31 ± 0.17) vs (0.17 ± 0.08) µU/mg, all P < 0.01), with no significance between CIH and CIH+Ad groups. The relative level of total reactive oxygen species (ROS) in genioglossus of CIH+Ad group was significantly lower than that in CIH group but higher than that in control group (1.94 ± 1.01 vs 3.31 ± 1.56 and 1.08 ± 0.38 all P < 0.05). The transcription of NF-κB was significantly higher in CIH group than that in control and CIH+Ad groups (2.24 ± 0.34 vs 0.78 ± 0.21, P < 0.05), but there was no statistical difference with CIH+Ad group (1.04 ± 0.27). CONCLUSION: CIH may induce oxidative stress and inflammation possibly through NF κB pathway while a supplement of Ad attenuates the above CIH-induced responses.

Adiponectin alleviates genioglossal mitochondrial dysfunction in rats exposed to intermittent hypoxia.

BACKGROUND: Genioglossal dysfunction is involved in the pathophysiology of obstructive sleep apnea hypoxia syndrome (OSAHS) characterized by nocturnal chronic intermittent hypoxia (CIH). The pathophysiology of genioglossal dysfunction and possible targeted pharmacotherapy for alleviation of genioglossal injury in CIH require further investigation. METHODOLOGY/PRINCIPAL FINDINGS: Rats in the control group were exposed to normal air, while rats in the CIH group and CIH+adiponectin (AD) group were exposed to the same CIH condition (CIH 8 hr/day for 5 successive weeks). Furthermore, rats in CIH+AD group were administrated intravenous AD supplementation at the dosage of 10 µg, twice a week for 5 consecutive weeks. We found that CIH-induced genioglossus (GG) injury was correlated with mitochondrial dysfunction, reduction in the numbers of mitochondrias, impaired mitochondrial ultrastructure, and a reduction in type I fibers. Compared with the CIH group, impaired mitochondrial structure and function was significantly improved and a percentage of type I fiber was elevated in the CIH+AD group. Moreover, compared with the control group, the rats' GG in the CIH group showed a significant decrease in phosphorylation of LKB1, AMPK, and PGC1-α, whereas there was significant rescue of such reduction in phosphorylation within the CIH+AD group. CONCLUSIONS: CIH exposure reduces mitochondrial biogenesis and impairs mitochondrial function in GG, while AD supplementation increases mitochondrial contents and alleviates CIH-induced mitochondrial dysfunction possibly through the AMPK pathway.

Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage.

Macrophage death in advanced atherosclerosis promotes plaque necrosis and destabilization. Involvement of autophagy in bulk degradation of cellular components has been recognized recently as an important mechanism for cell survival under endoplasmic reticulum (ER) stress. We previously found that the engagement of class A scavenger receptor (SR-A) triggered JNK-dependent apoptosis in ER-stressed macrophages. However, pro-apoptotic mechanisms mediated by SR-A are not fully understood. Therefore, we sought to see if SR-A mediated apoptosis was associated with autophagy in macrophages. Here, we showed that fucoidan inhibited microtubule-associated protein light chain 3-phospholipid conjugates (LC3-II) formation as well as the number of autophagosomes under ER stress. The inhibition of LC3-II formation was paralleled by the activation of the mTOR pathway, and the inhibition of mTOR allowed LC3-II induction in macrophages treated with thapsigargin plus fucoidan. Furthermore, apoptosis induced by fucoidan was prevented under ER stress by the mTOR inhibitor. We propose that fucoidan, a SR-A agonist, may contribute to macrophage apoptosis during ER stress by inhibiting autophagy.

Correlation of obstructive sleep apnea hypopnea syndrome with metabolic syndrome in snorers.

Though obstructive sleep apnea hypopnea syndrome (OSAHS) and metabolic syndrome (MS) are correlated; the contributing factors for the occurrence of MS in Chinese snorers remain largely undefined. We aimed to investigate the associated pathogenesis of coexistence of OSAHS and MS in Chinese snorers. A total of 144 Chinese habitual snorers were divided into 3 groups, the control group (simple snorers) (n  =  36), the mild OSAHS group (n  =  52) and the moderate-to-severe OSAHS group (n  =  56). The incidence of MS in the moderate-to-severe OSAHS group (26.8%) was significantly higher than that in the control group (8.3%), the mild OSAHS group (11.1%) and all the OSAHS patients (19.45%) (all P < 0.05). Homeostatic model assessment (HOMA) index and proinsulin (PI) were negatively correlated with nocturnal meanSpO2 and miniSpO2. Meanwhile, nocturnal SpO2 were negatively correlated with body mass index, waist and neck circumferences and diastolic blood pressure, but positively correlated with total cholesterol and high-density lipoprotein cholesterol. The study indicated that in Chinese snorers, moderate-to-severe OSAHS was closely associated with MS via nocturnal hypoxemia.

Adiponectin protects rat myocardium against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.

Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders such as heart failure, hypertension, atherosclerosis, and arrhythmia and so on. Of the many associated factors, chronic intermittent hypoxia (CIH) in particular is the primary player in OSAS. To assess the effects of CIH on cardiac function secondary to OSAS, we established a model to study the effects of CIH on Wistar rats. Specifically, we examined the possible underlying cellular mechanisms of hypoxic tissue damage and the possible protective role of adiponectin against hypoxic insults. In the first treatment group, rats were exposed to CIH conditions (nadir O2, 5-6%) for 8 hours/day, for 5 weeks. Subsequent CIH-induced cardiac dysfunction was measured by echocardiograph. Compared with the normal control (NC) group, rats in the CIH-exposed group experienced elevated levels of left ventricular end-systolic dimension and left ventricular end-systolic volume and depressed levels of left ventricular ejection fraction and left ventricular fractional shortening (p<0.05). However, when adiponectin (Ad) was added in CIH + Ad group, we saw a rescue in the elevations of the aforementioned left ventricular function (p<0.05). To assess critical cardiac injury, we detected myocardial apoptosis by Terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) analysis. It was showed that the apoptosis percentage in CIH group (2.948%) was significantly higher than that in NC group (0.4167%) and CIH + Ad group (1.219%) (p<0.05). Protein expressions of cleaved caspase-3, cleaved caspase-9, and cleaved-caspase-12 validated our TUNEL results (p<0.05). Mechanistically, our results demonstrated that the proteins expressed with endoplasmic reticulum stress and the expression of reactive oxygen species (ROS) were significantly elevated under CIH conditions, whereas Ad supplementation partially decreased them. Overall, our results suggested that Ad augmentation could improve CIH-induced left ventricular dysfunction and associated myocardial apoptosis by inhibition of ROS-dependent ER stress.

Adiponectin alleviates contractile dysfunction of genioglossus in rats exposed to chronic intermittent hypoxia.

BACKGROUND: Genioglossal dysfuntion takes an important role in pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) in which chronic intermittent hypoxia (CIH) is the major pathological origin. Recent studies have suggested genioglossal injury induced by CIH might be improved by adiponectin. The aim of this study was to investigate the effects of adiponectin on genioglossus contractile properties in rats exposed to CIH. METHODS: Thirty-nine healthy male Wistar rats were randomly divided into three groups: normal control (NC), CIH and adiponectin supplement (CIH+Ad) with 13 rats in each. Rats in NC were kept breathing normal air, while rats in CIH and CIH+Ad experienced the same CIH environment eight hours per day for 35 successive days. Rats in CIH+Ad were given intravenous adiponectin of 10 µg twice a week for 30 successive days. Rats in the NC and CIH were injected with normal saline as a control. After 35 days' CIH exposure, the levels of serum adiponectin and genioglossus contractile properties were compared. RESULTS: Serum adiponectin level was significantly lower in CIH than in NC (1210 ng/ml vs. 2236 ng/ml). Serum adiponectin level in CIH+Ad (1844 ng/ml) was significantly higher than CIH but lower than NC. Twitch tension, time to peak tension, half relaxation time and tetanic tension were significantly lower in CIH than NC and improved in CIH+Ad. All mean tetanic fatigue indices decreased more rapidly in the first 20 seconds than during the subsequent 100 seconds. Tetanic fatigue indices in NC and CIH+Ad were significantly higher compared to CIH. CONCLUSIONS: CIH could lead to hypoadiponectinaemia, impaired genioglossus contractile properties and decreased fatigue resistance in rats. Such changes could be partially offset by supplementation of adiponectin.

Adiponectin protects the genioglossus of rats against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome, characterized by chronic intermittent hypoxia (CIH), is closely correlated with genioglossus dysfunction. CIH has been identified to mediate mitochondrial damage in genioglossus. It has been reported that endoplasmic reticulum stress (ERS) could be induced by mitochondrial dysfunction. This study aimed to investigate the role of ERS in CIH-induced genioglossus injury, as well as the possible intervention effect of adiponectin (Ad) supplement in rats. METHODS: Forty-five male Wistar rats were randomly divided into three groups and submitted to room air (group A, n=15) as a control or CIH (groups B and C, n=15, respectively). Throughout the exposure period, intravenous Ad was given in group C; while intravenous normal saline was simultaneously given in groups A and B. After 35-day exposure, genioglossus samples were obtained from the pentobarbital-anaesthetized rats via surgical dissection, following blood sampling. Western blotting was applied to detect expressions of ERS signals and associated apoptotic pathways in genioglossus. Serum adiponectin levels were assessed via enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant hypoadiponectinemia was revealed in group B only (P < 0.05). Compared to those in groups A and C, expressions of markers involved in ERS, such as glucose regulated protein 78 (GRP78), p-PERK, phosphorylated eukaryotic initiation factor 2a (p-eIF2a), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1a (p-IRE1a), spliced X-Box binding protein 1 (XBP1s) and activating transcription factor 6 (ATF6), were significantly enhanced in group B (all P < 0.01); while no significant difference was shown between groups A and C (all P > 0.05). ERSassociated apoptotic pathways were remarkably activated in group B. The involved markers detected as the expression of CCAAT/enhancer binding protein homologous protein (CHOP), B-cell lymphoma/leukemia associatied X protein (BAX) and caspase-12 were significantly elevated (all P < 0.01). Transvenous adiponectin supplement improved the above CIHinduced pathological changes in group C. CONCLUSION: Beyond hypoadiponectinemia, CIH could enhance ERS and induce activation of ERS-associated apoptotic pathways in genioglossus, which could be significantly improved by adiponectin supplement.

Prevalence and risk factors of sleep disordered breathing in patients with rheumatic valvular heart disease.

STUDY OBJECTIVES: Sleep disordered breathing (SDB) is common in patients with chronic heart failure secondary to non-valvular heart disease; however, the prevalence and characteristics of SDB in patients with rheumatic valvular heart disease (RVHD) are unclear. This study was designed to determine the prevalence, characteristics, and risk factors for SDB in RVHD patients. METHODS: A cross-sectional study was conducted in 260 RVHD patients. The following data were recorded: types of heart valve lesions, electrocardiographic, echocardiographic, arterial blood gas analysis findings, baseline medication, 6-minute walk test (6MWT) distance, and sleep parameters. RESULTS: Compared to patients with single leftsided valve lesions, patients with left- and rightsided valve lesions had a higher prevalence of SDB (46.2% vs. 31.2%, p = 0.013); the increased prevalence of SDB only involved central sleep apnea (CSA) (31.1% vs. 14.1%, p = 0.001). Patients with obstructive sleep apnea (OSA) or CSA were older and had a shorter 6MWT distance, lower left ventricle ejection fraction and PaO2, a longer lung-to-finger circulation time, and a higher prevalence of atrial fibrillation (AF) and hypertension (all p < 0.05) as compared with patients without SDB. Multinomial logistic regression analysis showed that PaO2 ≤ 85 mm Hg was the only risk factor for OSA. Male gender, AF, 6MWT distance ≤ 300 m, PaO2 ≤ 85 mmHg, and PaCO2 ≤ 40 mm Hg were risk factors for CSA. CONCLUSIONS: Patients with RVHD had a high prevalence of SDB (predominantly CSA). RVHD patients with SDB, particularly those who had CSA, manifested more severe symptoms and greater impairment of cardiac function. Assessments of clinical manifestations of cardiac dysfunction may be important for predicting the risk factors for SDB.

A preliminary study on correlation between adiponectin genotype polymorphisms and obstructive sleep apnea hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) is regarded as a disease with strong genetic background and associated with hypoadiponectinemia. It is worthwhile to investigate the possible correlation between the single nucleotide polymorphisms (SNPs) in the adiponectin gene and OSAHS. METHODS: With the TaqMan polymerase chain reaction (PCR) method, the SNPs at positions 45 and 276 in the adiponectin gene were determined in Chinese of Han nationality in Nanjing district consisting of 103 OSAHS patients (OSAHS group) and 67 normal controls (control group). The association of adiponectin genotype polymorphisms at positions 45 and 276 with OSAHS was analyzed. RESULTS: No evidence of a direct association was found between OSAHS and adiponectin genotype SNP at positions 45 and 276 (P > 0.05). However, compared with those OSAHS patients having G/T + T/T genotype at position 276, the OSAHS patients with G/G genotype showed a longer neck circumference, a prolonged duration of the longest apnea event, and an elevated level of blood cholesterol and low-density lipoprotein cholesterol (P < 0.05). CONCLUSIONS: No direct association was suggested between OSAHS and adiponectin genotype distribution at positions 45 and 276 in Chinese of Han nationality in Nanjing district. However, in OSAHS patients, those with adiponectin G/G genotype at position 276, seemed to have a higher potential risk in development of OSAHS than those having adiponectin SNP276 G/T + T/T genotype.

Effects of chronic intermittent hypoxia on genioglossus in rats.

OBJECTIVE: The objective of this study was to investigate the effects of chronic intermittent hypoxia (CIH) on genioglossal ultrastructure and mitochondrial function as well as the intervention role of adiponectin (Ad). METHODS: Forty-two Wistar rats were randomly divided into three groups with 14 rats in each. Rats in group A were kept breathing normal air, while rats in both groups B and C received the same CIH environment (a 2-min cycle, 1 min on, 1 min off with a nadir O(2) at 4-5%, 8 h/day for successive 5 weeks). However, rats in group C was given regular intravenous Ad injection (10 µg per time, twice a week for successive 5 weeks). A simultaneous intravenous injection of saline (0.5 ml per time) was carried in groups A and B. At the end of experiment, the genioglossal ultrastructure, the serum adiponectin levels, the mitochondrial membrane potential (ΔΨ(m)), and activities of respiratory chain complexes I and IV in mitochondrion of genioglossal cells were compared among groups. RESULTS: Serum Ad level was significantly lower in group B than that in group A (P < 0.01). In group B, there were genioglussal myofibril discontinuities, lysis of myofilament, edema of mitochondria, and disruption of cristae, vacuolus, and lysis of some mitochondria. These pathological changes were less significant in group C. The relative value of ΔΨ(m) was the lowest in group B but the highest in group A (P < 0.01), with group B in between. The concentrations of mitochondrial complexes I and IV in group B were the lowest but became higher and higher from group C to A, with a significant difference among groups (all P < 0.05). CONCLUSION: CIH could lead to hypoadiponectinemia, impaired genioglossal ultrastructure, and mitochondrial dysfunction. These changes could be improved by supplement of Ad.

Caveolae-dependent endocytosis is required for class A macrophage scavenger receptor-mediated apoptosis in macrophages.

SR-A (class A macrophage scavenger receptor) is a transmembrane receptor that can bind many different ligands, including modified lipoproteins that are relevant to the development of vascular diseases. However, the precise endocytic pathways of SR-A/mediated ligands internalization are not fully characterized. In this study, we show that the SR-A/ligand complex can be endocytosed by both clathrin- and caveolae-dependent pathways. Internalizations of SR-A-lipoprotein (such as acLDL) complexes primarily go through clathrin-dependent endocytosis. In contrast, macrophage apoptosis triggered by SR-A-fucoidan internalization requires caveolae-dependent endocytosis. The caveolae-dependent process activates p38 kinase and JNK signaling, whereas the clathrin-mediated endocytosis elicits ERK signaling. Our results suggest that different SR-A endocytic pathways have distinct functional consequences due to the activation of different signaling cascades in macrophages.