The characteristics of microbiome in the upper respiratory tract of COVID-19 patients.

BACKGROUND: Co-infection with other pathogens in coronavirus disease 2019 (COVID-19) patients exacerbates disease severity and impacts patient prognosis. Clarifying the exact pathogens co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is premise of the precise treatment for COVID-19 patients. METHODS: Sputum samples were collected from 17 patients in the COVID-19 positive group and 18 patients in the COVID-19 negative group. DNA extraction was performed to obtain the total DNA. Sequencing analysis using 16S and ITS rRNA gene was carried out to analyze the composition of bacterial and fungal communities. Meanwhile, all the samples were inoculated for culture. RESULTS: We did not observe significant differences in bacterial composition between the COVID-19 positive and negative groups. However, a significantly higher abundance of Candida albicans was observed in the upper respiratory tract samples from the COVID-19 positive group compared to the COVID-19 negative group. Moreover, the Candida albicans strains isolated from COVID-19 positive group exhibited impaired secretion of aspartyl proteinases. CONCLUSION: COVID-19 positive patients demonstrate a notable increase in the abundance of Candida albicans, along with a decrease in the levels of aspartyl proteinases, indicating the alteration of microbiota composition of upper respiratory tract.

Peroxymonosulfate Activation by Cu-OMS-2 Nanofibers for Efficient Degradation of N-Containing Heterocycles in Aquatic Solution.

In this research, the degradation of different types of N-containing heterocycle (NHC) contaminants by Cu-OMS-2 via peroxymonosulfate (PMS) activation in an aqueous environment was investigated. First, the effects of different reaction parameters were optimized using benzotriazole (BTR) as the model contaminant, and the optimal reaction conditions were 8 mM PMS, 0.35 g/L Cu-OMS-2, and 30 °C. Nine different types of NHC contaminants were effectively degraded under these reaction conditions, and the degradation efficiencies and the mineralization rates of those NHCs were more than 68 and 46%, respectively. Moreover, the Cu-OMS-2/PMS process presented excellent performance at a wide pH ranging from 3.0 to 11.0 and in the presence of some representative anions (NO3- and SO42-) and dissolved organic matter (fumaric acid). The inhibition sequence of anions on BTR removal during the Cu-OMS-2/PMS process was H2PO4- > HCO3- > Cl- > CO32- > NO3- > SO42-. It was also found that 74.5 and 71.3% BTR degradation rates were achieved in actual water bodies, such as tap water and Yellow River water, respectively. Besides, the Cu-OMS-2 heterogeneous catalyst had excellent stability and reusability, and the degradation rate of BTR was still at 77.0% after 5 cycles. Finally, electron paramagnetic resonance analysis and scavenging tests showed that 1O2 and SO4- • were the primary reactive oxygen species. Accordingly, Cu-OMS-2 nanomaterial was an efficient and sustainable heterogeneous catalyst to activate PMS for the decontamination of BTR in water remediation.

Characteristics of phenotypic antibiotic resistance of Helicobacter pylori and its correlation with genotypic antibiotic resistance: A retrospective study in Ningxia.

BACKGROUND: Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance. METHODS: Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby-Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed. RESULTS: We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement. CONCLUSION: H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.

First Report of Valsa nivea (Hoffm.) Fr. Causing Valsa Canker on Korla Pear (Pyrus sinkiangensis Yü) in the World.

Korla pear (Pyrus sinkiangensis Yü) is an important commercial fruit tree that originated in China (Zhou et al. 2020). In April 2020, a survey was conducted in Aksu region, Xinjiang (40°55'37"N, 80°28'42"E), China. Some Korla pear trees (>15 years old) exhibited symptoms of branch dieback and branch cankers. Cankers observed on the trunk and branches of the tree were sunken, dark ulcerative lesions sometimes exhibiting signs of stromata erumpent through the bark and exuding yellow to reddish-orange spore tendrils. Of the 180 plants surveyed, 80% were symptomatic. Thirty samples of symptomatic tissues of infected branches were taken to the laboratory. Bark and cortical wood samples containing necrotic and healthy tissue were excised with flame-sterilized scalpels, surface disinfected with 75% ethanol and 1% NaClO, placed on PDA plates, and incubated at 25°C. A total of 30 fungal isolates were obtained. Among them, 28 isolates were identified as Valsa mali var. pyri (Lu. 1992) based on morphological and molecular identification, and two isolates (ALE6T-GP21 and ALE7T-GP23) were identified as Valsa nivea (Hoffm.) Fr. Valsa nivea isolates had a fine villi form mycelium that was initially white, turned grayish-green over time and grew close to the medium surface. Cultures also contained black ostiolate pycnidia in a stroma that consisted of multiple irregular locules. Conidiophores were hyaline, occasionally branched at the bases and (15.50-)16.48-17.94(-18.50)×(1.00-)1.13-1.37(-1.50) µm (n=20). Conidiogenous cells were phialidic and subcylindrical that taper towards the apex. Conidia were hyaline, banana-like and (5.47-)6.13-6.97(-7.64)×(1.02-)1.06-1.20(-1.23) µm (n=10). The molecular characteristics are consistent with the previous description of V. nivea (Adams et al. 2006). The internal transcribed spacer (ITS), transcription elongation factor (tef-1α) and ß-tubulin (Tub2) gene were sequenced using ITS1/ITS4, EF1-728F/EF1-986R and Bt2a/Bt2b primers, respectively (Zhang et al. 2014). BLAST (Basic Local Alignment Search Tool) searches against the NCBI database revealed that the ITS sequence had 99.83% homology (ON843984.1 and ON843987.1), tef-1α gene had 99.22% homology (MH015266.1 and MH015267.1), and the Tub2 sequence had 99.57% and 100% homologies (KT934364.1 and KT934364.1) with V. nivea sequences. The amplified sequences of ITS region (OK442665 and OK442666), tef-1α (OK510871 and OK510872) and Tub2 (OK510869 and OK510870) were deposited in the GenBank. A phylogenetic analysis was performed using MEGA7 that shows 100% bootstrap support that ALE6T-GP21 and ALE7T-GP23 were V. nivea. A pathogenicity trial was conducted with isolate ALE6T-GP21 inoculated onto 1-year-old shoots of 15-year-old Korla pear trees in Alar city, Xinjiang, China. Five shoots were inoculated by making 5-mm deep wounds using a sterile scalpel then inoculating with a 50 µL conidia suspension (1×106 mL-1). Additionally, five shoots served as the negative control and were inoculated in the same way using 50 µL ddH2O. The trees were kept under ambient conditions. Inoculated branches developed symptoms 18 days post inoculation, whereas the control branches showed no symptoms. V. nivea was re-isolated from the symptomatic areas and the isolate confirmed as ALE6T-GP21 by sequence analysis. Currently, the proven hosts of V. nivea are Populus, Elaeagnus, Juglans, Malus and Salix (Adams et al. 2006; Wang et al. 2020). To our knowledge, this is the first report of pathogenic V. nivea occurring on P. sinkiangensis in the world. It will provide a basis for research into the occurrence, distribution of V. nivea on Korla Pear.

Globular adiponectin protects hepatocytes against intermittent hypoxia-induced injury via Pink1/Parkin-mediated mitophagy induction.

PURPOSE: This study sought to determine the effect of Pink1/Parkin-mediated mitophagy on liver cells exposed to intermittent hypoxia (IH) and the roles of globular adiponectin (gAPN). METHODS: The hepatocyte model of IH was established. Cell apoptosis was assessed using flow cytometry. Mitochondrial membrane potential (MMP) level was determined using JC-1, and mitophagy was assessed using a confocal laser. Mitochondrial injury associated protein levels of bax and bcl-2, and protein levels of Pink1 and Parkin were evaluated via western blotting. We downregulated Parkin expression by transfecting the cells with Parkin siRNA. RESULTS: Pink1 and Parkin protein levels, mitophagy, and cell apoptosis rate were high, while the MMP level and protein level ratio of bcl-2/bax were low in IH-treated hepatocyte. gAPN upregulated Pink1 and Parkin protein levels, MMP level, protein level ratio of bcl-2/bax, and mitophagy while it reduced the rate of cell apoptosis in IH-treated hepatocytes. Inhibiting Parkin expression significantly reduced mitophagy and increased mitochondrial injury and the rate of hepatocyte apoptosis under IH or IH with gAPN. CONCLUSION: gAPN alleviated IH-induced mitochondrial injury and hepatocyte apoptosis by upregulating Pink1/Parkin-mediated mitophagy.

Adiponectin ameliorates lung injury induced by intermittent hypoxia through inhibition of ROS-associated pulmonary cell apoptosis.

PURPOSE: Obstructive sleep apnea hypopnea syndrome has been reported to be associated with pulmonary hypertension (PH). Adiponectin (Ad) has many protective roles in the human body, including its function as an anti-inflammatory and an anti-oxidant, as well as its role in preventing insulin resistance and atherosclerosis. This study aimed to investigate the molecular mechanism of chronic intermittent hypoxia (CIH)-induced pulmonary injury and the protective role of Ad in experimental rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into three groups with 10 rats in each group: normal control (NC) group, CIH group, and CIH + Ad group. Rats in the NC group were kept breathing room air for 12 weeks. Rats in the CIH group were intermittently exposed to a hypoxic environment for 8 h/day for 12 weeks. Rats in the CIH + Ad group received 10 µg Ad twice weekly via intravenous injection. After 12 weeks of CIH exposure, we detected the pulmonary function, pulmonary artery pressure, lung histology, pulmonary cell apoptosis, pulmonary artery endothelial cell apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) level. We also analyzed expression proteins involved in the mitochondria-, endoplasmic reticulum (ER) stress-, and Fas receptor-associated pulmonary apoptosis pathways, as well as the SIRT3/SOD2 pathway. RESULTS: CIH exposure for 12 weeks did not lead to abnormal pulmonary function, PH, or pulmonary artery endothelial cell apoptosis. However, we observed a significant increase in the rate of pulmonary cell apoptosis, the expression of proteins involved in mitochondria-, ER stress-, and Fas receptor-associated pulmonary apoptosis pathways, and the generation of ROS in the CIH group compared with the NC group. In contrast, the MMP and protein expressions of SIRT3/SOD2 pathway were significantly decreased in the CIH group compared with the NC group. Ad supplementation in the CIH + Ad group partially improved these changes induced by CIH. CONCLUSION: Even though CIH did not cause abnormal pulmonary function or PH, early lung injury was detected at the molecular level in rats exposed to CIH. Treatment with Ad ameliorated the pulmonary injury by activating the SIRT3/SOD2 pathway, reducing ROS generation, and inhibiting ROS-associated lung cell apoptosis.

The rate of decrease in oxygen desaturation during severe obstructive sleep apnea syndrome is correlated with subjective excessive daytime sleepiness.

PURPOSE: To explore factors that influence subjective excessive daytime sleepiness (EDS) in patients with severe obstructive sleep apnea syndrome (OSAS). METHODS: Patients with snoring seen at the Sleep Medicine Center of The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University between October 2018 and November 2019 were included in this study. All patients underwent polysomnography (PSG). Noninvasive frequency-domain analysis was used to assess the autonomic nervous system regulation of the heart, with the low frequency (LF)/high frequency (HF) power ratio used to represent the sympathetic-parasympathetic balance. Daytime sleepiness was evaluated by the Epworth sleepiness scale (ESS). Overnight apnea episodes were included for analyses. The rate of pulse oxyhemoglobin saturation (SpO2) decrease was measured as the change in the percentage of SpO2 per second after obstructive apnea and was expressed as the oxygen desaturation rate (ODR). RESULTS: A total of 101 patients with severe OSAS were enrolled in this study and were further divided into two groups: the EDS group (ESS > 10, n = 52) and the non-EDS group (ESS ≤ 10, n = 49). The apnea-hypopnea index (AHI), respiratory effort-related arousals (RERAs), and LF/HF power ratio were significantly higher in the EDS group than in the non-EDS group (AHI: 69.9 ± 14.5 vs. 57.9 ± 16.1 events/h; RERAs: 42.2 ± 16.7 vs. 30.4 ± 13.7 events/h; LF/HF power ratio: 2.9 ± 0.8% vs. 2.4 ± 0.9%, all p < 0.001). Multiple linear regression analyses revealed that after adjusting for covariates expected to affect this relationship, ESS scores were correlated with ODR (ß = 0.520, p < 0.001) and LF/HF power ratio (ß = 0.155, p = 0.028), rather than with the traditional sleep-disordered breathing parameters. CONCLUSIONS: Compared with the traditional PSG parameters, both ODR and an increased LF/HF power ratio were more closely related to daytime sleepiness, especially ODR.

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.

Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division.

Objective This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH). Methods Sixty rats were randomly divided into three groups: normal control (NC) group, CIH group, and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure, we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT), examined and compared the adenosine triphosphate (ATP) levels, mitochondrial membrane potential (MMP) levels, reactive oxygen species (ROS) levels, enzymes gene expression levels of Ant1, Cs, Hmox1, and Cox4i1 which represented mitochondrial tricarboxylic acid cycle function, the protein and gene expression levels of DRP1, FIS1, MFN1, and OPA1 which represented mitochondrial fusion and division, and the protein expression levels of BAX, BCL-2, cleaved Caspase-3, and cleaved PARP which represented mitochondrial associated apoptosis pathway of pancreatic islet. Results OGTT and IRT showed blood glucose and insulin levels had no differences among the NC, CIH and CIH+APN groups (both P>0.05) at 0 min, 20 min, 30 min, 60 min, 120 min. However, we found that compared to NC group, CIH increased the ROS level, reduced ATP level and MMP level. The islets of CIH exposed rats showed reduced gene expression levels of Ant1, Cs, Hmox1, and Cox4i1, decreased protein and gene expression levels of MFN1 and OPA1, increased protein and gene expression levels of DRP1 and FIS1, increased protein expression levels of cleaved Caspase-3 and cleaved PARP, with lower ratio of BCL-2/BAX at protein expression level. All the differences among three groups were statistically significant. APN treated CIH rats showed mitigated changes in the above measurements associated with islet injuries. Conclusion APN may ameliorate the pancreatic islet injury induced by CIH via inhibiting the imbalance in mitochondrial fusion and division.

CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain. METHODS: After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood. RESULTS: Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood. CONCLUSIONS: Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .).

Comparison between auto-trilevel and bilevel positive airway pressure ventilation for treatment of patients with concurrent obesity hypoventilation syndrome and obstructive sleep apnea syndrome.

PURPOSE: Our study aims to compare the difference in clinical efficacy between auto-trilevel positive airway pressure (auto-trilevel PAP) ventilator and conventional fixed bilevel positive airway pressure (BiPAP) ventilator for obesity hypoventilation syndrome (OHS) patients with coexisting moderate or severe obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Twenty-three OHS patients with moderate or severe OSAHS enrolled between January 2015 and September 2017 underwent ventilation by three different modes of positive airway pressure (PAP) for 8 h per night. A single variable mode was applied at the first night followed by two nights when no PAP therapy was carried out as a washout period between each mode. The inspiratory positive airway pressure (IPAP) decided by PaCO2 was consistently used for modes 1, 2, and 3. In mode 1, the expiratory positive airway pressure (EPAP) issued by BiPAP was decided by the minimal PAP levels for cessation of snoring. However, in mode 2, the EPAP was fixed at 3 cmH2O higher than this value. With the use of auto-trilevel PAP in mode 3, the EPAP was set to initially match that of mode 1 but the end of EPAP (EEPAP) was automatically regulated to be elevated according to upper airway patency condition. We also compared the following parameters including apnea hypopnea index (AHI), minimal SpO2 (miniSpO2), arousal index, and sleep efficiency during sleep; PaCO2 in the morning and Epword sleepiness score (ESS) at daytime were measured prior to and during PAP treatment as well as between three selected PAP modes. RESULTS: Compared with the parameters before ventilation therapies, all three variable modes of ventilation were associated with a higher nocturnal miniSpO2 and sleep efficiency (all P < 0.01). Among the three variable modes, mode 3 resulted in not only the lowest arousal index and daytime ESS but also the highest sleep efficiency. Compared to mode 1, mode 2 demonstrated a significantly reduced AHI and an elevated miniSpO2 and morning PaCO2 (all P < 0.05), while mode 3 was associated with a decreased AHI, an increased miniSpO2 (all P < 0.05), and no statistical change of PaCO2 following the end of PAP treatment (P > 0.05). Comparison between mode 2 and mode 3 revealed that mode 3 had a significantly lower PaCO2 (P < 0.05), but displayed no remarkable changes of AHI and miniSpO2 (all P > 0.05). CONCLUSION: Compared to fixed BiPAP ventilation, auto-trilevel PAP ventilation could more effectively correct hypercapnia, achieve lower index of nocturnal apnea and hypopnea, more improved sleep quality, and lower daytime sleepiness score. Auto-trilevel PAP ventilation is therefore more efficacious than conventional BiPAP ventilation in non-invasive ventilation therapy for OHS patients with concurrent moderate or severe OSAHS.

Inducers of post-apneic blood pressure fluctuation monitored by pulse transfer time measurement in obstructive sleep apnea varied with syndrome severity.

PURPOSE: This study investigated the properties of blood pressure (BP) fluctuation and sympathovagal imbalance with the severity of OSAS. METHODS: Nocturnal BP was continuously monitored by polysomnography for mild (n = 33), moderate (n = 34), and severe (n = 37) OSAS patients. Apnea-related systolic BP elevation (△SBP) indicated the amplitude of BP fluctuation. The SBP index, number of △SBP > 10 mmHg/h of sleep, indicated the frequency of significant BP fluctuations. The low frequency/high frequency (LF/HF) ratios indicated heart rate variability and sympathovagal imbalance. RESULTS: △SBP and the SBP index were the highest in severe OSAS (12.9 ± 2.3 mmHg and 33.7 ± 14.7/h), followed by moderate OSAS (9.5 ± 2.6 mmHg and 7.1 ± 4.4/h), and mild OSAS (8.3 ± 1.6 mmHg and 3.4 ± 2.1/h). The LF/HF ratios in severe OSAS were significantly higher than that in moderate and mild OSAS. In mild OSAS, arousal played a more important role in BP fluctuation. In moderate OSAS, the oxygen desaturation index (ODI) and the SBP index were correlated. The difference in △SBP induced by hypoxia or by arousal was not significant. In severe OSAS, the apnea-hypopnea index (AHI) and LF/HF ratio were correlated with the SBP index, and △SBP was larger with hypoxia than arousal. CONCLUSIONS: BP fluctuation and sympathovagal imbalance were both related to obstructive sleep apnea severity. The influence of arousal and hypoxia on BP fluctuation varied with OSAS severity. TRIAL REGISTRATION: NCT02876471.

Auto-trilevel versus bilevel positive airway pressure ventilation for hypercapnic overlap syndrome patients.

PURPOSE: Although bilevel positive airway pressure (Bilevel PAP) therapy is usually used for overlap syndrome (OS), there is still a portion of OS patients in whom Bilevel PAP therapy could not simultaneously eliminate residual apnea events and hypercapnia. The current study was expected to explore whether auto-trilevel positive airway pressure (auto-trilevel PAP) therapy with auto-adjusting end expiratory positive airway pressure (EEPAP) can serve as a better alternative for these patients. METHODS: From January of 2014 to June of 2016, 32 hypercapnic OS patients with stable chronic obstructive pulmonary diseases (COPD) and moderate-to-severe obstructive sleep apnea syndrome (OSAS) were recruited. Three variable modes of positive airway pressure (PAP) from the ventilator (Prisma25ST, Weinmann Inc., Germany) were applicated for 8 h per night. We performed the design of each mode at each night with an interval of two nights with no PAP treatment as a washout period among different modes. In Bilevel-1 mode (Bilevel-1), the expiratory positive airway pressure (EPAP) delivered from Bilevel PAP was always set as the lowest PAP for abolishment of snoring. For each patient, the inspiratory positive airway pressure (IPAP) was constantly set the same as the minimal pressure for keeping end-tidal CO2 (ETCO2) ≤45 mmHg for all three modes. However, the EPAP issued by Bilevel PAP in Bilevel-2 mode (Bilevel-2) was kept 3 cmH2O higher than that in Bilevel-1. In auto-trilevel mode (auto-trilevel) with auto-trilevel PAP, the initial part of EPAP was fixed at the same PAP as that in Bilevel-1 while the EEPAP was automatically regulated to rise at a range of ≤4 cmH2O based on nasal airflow wave changes. Comparisons were made for parameters before and during or following treatment as well as among different PAP therapy modes. The following parameters were compared such as nocturnal apnea hypopnea index (AHI), minimal SpO2 (minSpO2), arousal index, sleep structure and efficiency, morning PaCO2, and daytime Epworth Sleepiness Scale (ESS). RESULTS: Compared with the parameters before PAP therapies, during each mode of PAP treatment, significant reduction was detected in nocturnal AHI, arousal index, morning PaCO2, and daytime ESS while significant elevation was revealed in nocturnal minSpO2 and sleep efficiency (all P < 0.01). Comparison among three PAP modes indicated that under the same IPAP, the auto-trilevel PAP mode could result in the lowest arousal index, daytime ESS, and the highest sleep efficiency. Compared with Bilevel-1, it was detected that (a) AHI was lower but minSpO2 was higher in both Bilevel-2 and auto-trilevel (all P < 0.05) and (b) morning PaCO2 showed no statistical difference from that in auto-trilevel but displayed higher in Bilevel-2 (P < 0.05). Compared with Bilevel-2, in auto-trilevel, both AHI and minSpO2 showed no obvious changes (all P > 0.05) except with a lower morning PaCO2 (P < 0.05). CONCLUSION: Auto-trilevel PAP therapy was superior over conventional Bilevel PAP therapy for hypercapnic OS patients with their OSAS moderate to severe, since auto-trilevel PAP was more efficacious in synchronous elimination of residual obstructive apnea events and CO2 retention as well as in obtaining a better sleep quality and milder daytime drowsiness.

Nocturnal blood pressure fluctuation and associated influential factors in severe obstructive sleep apnea patients with hypertension.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) can induce dramatic blood pressure (BP) fluctuations during sleep and it can be associated with hypertension. We investigated the properties and associated influential factors of BP fluctuation in severe OSAS with and without hypertension. METHODS: Two hundred one severe OSAS subjects were divided into hypertensive and normotensive groups. BP was continuously monitored via measurement of pulse transmit time (PTT). The value of apnea-related systolic BP elevation (ΔSBP) was used to reflect the amplitude of BP fluctuation, and the SBP index (the number of ΔSBP > 10 mmHg per hour of sleep time) was used to stand for the frequency of significant BP fluctuations. RESULTS: Compared with the normotensive group, △SBP and SBP index were higher in the hypertensive group (13.8 ± 4.4 mmHg vs 10.9 ± 3.1 mmHg; 44.8 ± 21.3 events/h vs 26.8 ± 15.8 events/h, all p < 0.001). Multiple regression analysis showed that percentage of sleep time with oxygen saturation < 90% (TST90) and SBP index correlated more with mean level of awakeness and sleep SBP than with apnea-hypopnea index (AHI). Analysis of all apnea events demonstrated that △SBP and the frequency of BP fluctuations were more remarkable following hypoxia than following arousal; △SBP correlated more with oxygen desaturation degree (r = 0.388, p < 0.01) and minimal SpO2 (r = 0.392, p < 0.01) than with apnea length and desaturation duration. CONCLUSIONS: In severe OSAS, nocturnal and awake BP levels are associated more with the nocturnal hypoxic duration and BP fluctuation than with AHI. Nocturnal BP fluctuation can be induced by both hypoxia and arousal, and especially by hypoxia. TRIAL REGISTRATION: NCT02876471.

Adiponectin protects the kidney against chronic intermittent hypoxia-induced injury through inhibiting endoplasmic reticulum stress.

PURPOSE: The current study was carried out to assess the effects of chronic intermittent hypoxia (CIH) on the kidney, the intervention roles of adiponectin (Ad), and the associated mechanisms. METHODS: Sixty Wistar rats were randomly divided into four groups: the normal control (NC), normal control plus Ad supplement (NC + Ad), CIH, and CIH plus Ad supplement (CIH + Ad) groups. The rats in both CIH and CIH + Ad groups were submitted to a CIH environment for 4 months, while the rats in NC and NC + Ad groups were housed with the normal air for 4 months. In addition, the rats in NC + Ad and CIH + Ad groups were treated with an intravenous injection of Ad at a dosage of 10 µg per injection, twice a week, for four successive months. RESULTS: The production level of reactive oxygen species (ROS) and the protein levels of endoplasmic reticulum (ER) stress, as well as the cell apoptosis level in kidney, were all higher in the CIH group than in the NC and NC + Ad groups (all p < 0.05). However, the ROS production, the protein of ER stress, and cell apoptosis levels in kidney were all lower in the CIH + Ad group than those in the CIH group (all p < 0.05). CONCLUSION: Ad could protect against CIH-induced renal cell apoptosis through inhibiting ROS-related ER stress.

[Chemical constituents from Barringtonia racemosa].

To investigate the chemical constituents from Barringtonia racemosa, twelve compounds were isolated by chromatography methods and identified as 3ß-p-E-coumaroymaslinic acid (1), cis-careaborin (2), careaborin (3), maslinic acid (4), 2α, 3ß, 19α-trihydroxyolean-12-ene-24, 28-dioic acid (5), 3ß-p-Z-coumaroylcorosolic acid (6), corosolic acid (7), 1α, 2α, 3ß, 19α-tetrahydroxyurs-12-en-28-oic acid (8), 19α-hydroxyl ursolic acid (9), 3α, 19α-dihydroxyurs-12-en-24, 28-dioic acid (10), tormentic acid (11), 3-hydroxy-7, 22-dien-ergosterol（12） by the NMR and MS data analysis. Among them, compounds 1-4,7-12 were obtained from the genus Barringtonia for the first time. All the compounds didn't show nocytotoxic activity against MCF-7 and A549 cell lines (IC50>50 mg•L⁻¹).

[Occurrence and clinical characteristics of sleep apnea syndrome in heart failure patients with atrial fibrillation].

OBJECTIVE: To evaluate the occurrence and clinical characteristics of sleep apnea syndrome (SAS) in heart failure (HF) patients with atrial fibrillation (AF). METHODS: From HF patients hospitalized in the First Affiliated Hospital of Nanjing Medical University during June 2012 and June 2014, subjects were recruited based on electrocardiography examination, including 110 patients with AF (coexisting AF group) and 105 parallel control patients without AF but with matched age, gender and body mass index (simple HF group). Comparison was made about the occurrence and characteristics of SAS between two groups. RESULTS: There was no statistical difference in causes of HF, complications, New York Heart Association class and basic medication between two groups. Compared with the patients in simple HF group, the patients in coexisting AF group had a significantly higher Epworth sleepiness scale score, larger cardiothoracic ratio (10.1±5.8 vs 8.2±5.5, 0.63±0.08 vs 0.57±0.07; both P<0.05), and shorter 6-minute walk distance [(305±70) vs (335±69) m, P<0.05]. There was no difference in left ventricular ejection fraction, left ventricular end-diastolic dimension and left ventricular end-systolic dimension between two groups. However, left atrial diameter was remarkably larger in coexisting AF group than that in simple HF group (P<0.05). The prevalence of SAS was higher in coexisting AF group than that in simple HF group (36.4% vs 20.0%, P<0.05). Compared with simple HF group, the coexisting AF group had a higher apnea/hypopnea index [4(1, 16) vs 3(1, 7) times/h, P<0.05]. No significant differences were detected between two groups among the rapid of eye movement sleep stage/total sleep time, arousal index, mean and lowest pulse oxygen saturation (SpO2) and oxygen desaturation index. CONCLUSION: HF patients with AF have a higher frequency of SAS, more severe daytime sleepiness and poorer physical activity than matched simple HF patients without AF.

[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.

[Effects of continuous positive airway pressure treatment of inflammatory factors in patients with overlap syndrome].

OBJECTIVE: To explore the effects of continuous positive airway pressure (CPAP) treatment on the serum levels of associated inflammatory factors in patients with overlap syndrome (OS). METHODS: Seventy-four patients with obstructive sleep apnea syndrome (OSAS) or chronic obstructive pulmonary disease (COPD) or overlap syndrome (OS) were recruited from Department of Respirology and Affiliated Sleep Center of our hospital from March 2012 to September 2013. They were divided into OSAS (n = 25), COPD (n = 26) and OS (n = 23) groups according to the results of polysomnography (PSG) and spirometry. By enzyme linked immunosorbent assay (ELISA), the serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and asymmetric dimethylarginine (ADMA) were measured and compared before and at Day 30 post-CPAP in OSAS and OS groups. RESULTS: At pre-CPAP, there was no statistical difference in serum levels of CRP ((7.2 ± 6.6),(8.4 ± 6.8),(8.5 ± 7.9) mg/L) and TNF-α ((33 ± 13),(52 ± 34),(41 ± 33) ng/L) among OSAS, COPD and OS groups (all P > 0.05).However, serum ADMA level in OSAS group were significantly lower than those in COPD group ((0.50 ± 0.08) vs (0.71 ± 0.31) µmol/L, P = 0.002). Compared with before and at Day 30 post-CPAP, although no significant difference existed in serum levels of ADMA (all P > 0.05), at Day 30 post-CPAP there were significantly lower serum levels of CRP ((4.5 ± 4.2) and (5.5 ± 4.1) mg/L) and TNF-α levels ((31 ± 9) and (35 ± 24) ng/L) than those pre-CPAP in OSAS and OS groups respectively (all P < 0.05).No significant difference existed between OSAS and OS groups (all P > 0.05). CONCLUSION: CPAP treatment significantly reduces the serum levels of CRP and TNF-α so as to improve inflammation responses in OS and OSAS patients.

[Efficacies of stimulation of genioglossus in mild-to-moderate obstructive sleep apnea syndrome patients after uvulopalatopharyngoplasty].

OBJECTIVE: To evaluate the efficacies of transcutaneous stimulation of genioglossus on remaining mild-to-moderate obstructive sleep apnea syndrome (OSAS) after uvulopalatopharyngoplasty (UPPP). METHODS: A total of 22 patients diagnosed with mild-to-moderate OSAS by polysomnography (PSG) after UPPP were recruited from Sleep Center of First Affiliated Hospital, Nanjing Medical University from February 2013 to October 2013 and underwent transcutaneous stimulation of genioglossus therapy at night. Prior to and during treatment overnight polysomnography examination was performed. Moreover, the sleepiness of patients was assessed according to the Epworth sleepiness scale (ESS) before and after treatment. Comparison was made to observe the effects of treatment on PSG parameters and daytime ESS. RESULTS: Compared with pre-treatment, nocturnal apnea hypopnea index (AHI) (9.3 ± 4.2 vs 18.3 ± 6.8), microarousal index (MAI) (6.5 ± 3.8 vs 11.2 ± 4.8), radio of duration pulse oxygen saturation (SpO2) < 90% to total sleep time (T90) ((5.1 ± 4.0)% vs (9.5 ± 4.0)%) and score of daytime ESS (8.8 ± 3.3 vs 9.4 ± 3.1) all significantly decreased (all P < 0.01) while mean SpO2 ((95.5 ± 1.0)% vs (94.4 ± 1.1)%) and minimal SpO2 ((88.6 ± 2.9)% vs (84.9 ± 4.6)%) were both significantly elevated (both P < 0.001). None of them experienced obvious discomforts during treatment. CONCLUSION: Submental transcutaneous electrical stimulation of genioglossus is an effective treatment for remaining mild-to-moderate OSAS after UPPP surgery.