Association of ABCB1 polymorphisms with lipid homeostasis and liver injury response to atorvastatin in the Chinese population.

The present research was to assess the relationship between ABCB1 (G2677T/A, C3435T) polymorphisms and lipid homeostasis as well as risk of liver injury induced by atorvastatin in in-patients from China. The lipid levels (total cholesterol, high-density lipoprotein, triglycerides) as well as metabolic enzymes of hepar (glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, alkaline phosphatase, γ-glutamyl transpeptidase) in plasma for 162 patients were measured at baseline and after approximately 6 months of atorvastatin treatment. Polymorphisms of the ABCB1 gene were determined using the Snapshot technique. The associations between genetic polymorphisms and lipid levels as well as hepar indexes were evaluated at the end of medical treatment. Based on one-way ANOVA analysis, patients with the 2677GG or 3435TT genotypes showed a remarkable decrease in percentage when the level of TC was above 4.00 mmol·L-1, separately (P < 0.05). There was a significant decrease in percentage in the frequency of patients with the 2677GG genotype (low-density lipoprotein > 2.00 mmol·L-1) (P < 0.05). The level of glutamic-pyruvic transaminase in patients with the 2677GG or 3435CC genotype displayed a significantly increase in percentage, respectively (P < 0.05). The ABCB1 G-C haplotype carriers were associated with an increased risk of AILI. The results provide evidence for clinically individualised utilisation of atorvastatin for lipid homeostasis as well as risk of induced liver injury in the Chinese population.

A novel innexin2 forming membrane hemichannel exhibits immune responses and cell apoptosis in Scylla paramamosain.

Innexins are a class of transmembrane proteins that are important for embryonic development, morphogenesis and electrical synapse formation. In the present study, a novel innexin2 gene from Scylla paramamosain was named Sp-inx2 and characterized. The complete cDNA and genomic DNA sequences of Sp-inx2 were revealed. Sp-inx2 mRNA transcripts were distributed in various tissues of S. paramamosain and were most abundant in the hemocytes. The Sp-inx2 was significantly upregulated in hemocyte, gill and hepatopancreas tissues with the challenge of either Vibrio alginolyticus, Vibrio parahaemolyticus or lipopolysaccharides (LPSs) when analyzed at 3 and 6 h using quantitative real-time PCR, suggesting that it could activate an immune response against the challenge of LPSs or Vibrio species. Using the chemical inhibitors carbenoxolone and probenecid, the absorption of the fluorescent dye Lucifer yellow decreased in the primary cultured hemocytes of crabs, thus confirming that hemichannels composed of Sp-inx2 existed in the crab hemocytes. With LPS stimulation, the level of mRNA transcripts and protein expression of Sp-inx2 in the same cultured hemocytes gradually increased from 6 to 48 h, while the activity of hemichannels was down-regulated at 6 and 12 h, demonstrating that LPSs could modulate the absorption activity of hemichannels in addition to its upregulation of Sp-inx2 gene expression. Furthermore, the dye uptake rate in HeLa cells in which Sp-inx2 was ectopically expressed increased dramatically but the increase was significantly down-regulated with the addition of 50 µg mL(-1) LPS, suggesting that the LPS stimulation could effectively reduce the activity of hemichannels. Interestingly, with the ectopic expression of Sp-inx2 in HeLa and EPC cells, apoptosis spontaneously occurred in both cultured cell lines when detected using TUNEL assay. In summary, a new Sp-inx2 gene was first characterized in a marine animal S. paramamosain and it had a function associated with immune response and cell apoptosis.

Negative regulation of mTOR activity by LKB1-AMPK signaling in non-small cell lung cancer cells.

AIM: To investigate the role of LKB1 in regulation of mTOR signaling in non-small cell lung cancer (NSCLC) cells. METHODS: LKB1 protein expression and phosphorylation of AMPK, 4E-BP1 and S6K in the cells were assessed using Western blotting in various NSCLC cell lines (A549, H460, H1792, Calu-1 and H1299). Energy stress was mimicked by treating the cells with 2-deoxyglucose (2-DG). Compound C was used to inhibit AMPK activity. Cell growth was measured using the MTS assay. RESULTS: LKB1 protein was expressed in LKB1 wild-type Calu-1, H1299 and H1792 cells, but it was undetected in LKB1 mutant A549 and H460 cells. Treatment of the LKB1 wild-type cells with 2-DG (5, 10 and 25 mmol/L) augmented the phosphorylation of AMPK in dose- and time-dependent manners. In the LKB1 wild-type cells, 2-DG dramatically suppressed the phosphorylation of two mTOR targets, 4E-BP1 and S6K, whereas the LKB1 mutant A549 and H460 cells were highly resistant to 2-DG-induced inhibition on mTOR activity. In addition, stable knockdown of LKB1 in H1299 cells impaired 2-DG-induced inhibition on mTOR activity. Pretreatment of H1299 and H1792 cells with the AMPK inhibitor compound C (10 µmol/L) blocked 2-DG-induced inhibition on mTOR activity. 2-DG inhibited the growth of H1299 cells more effectively than that of H460 cells; stable knockdown of LKB1 in H1299 cells attenuated the growth inhibition caused by 2-DG. CONCLUSION: In non-small cell lung cancer cells, LKB1/AMPK signaling negatively regulates mTOR activity and contributes to cell growth inhibition in response to energy stress.

[A preliminary study on the measurement of (1,3)-ß-D-glucan in bronchoalveolar lavage for the diagnosis of pulmonary fungal infections].

OBJECTIVE: To explore the measurement of (1,3)-ß-D-glucan bronchoalveolar lavage fluid (BALF) for the diagnosis of pulmonary fungal infections. METHODS: A total of 135 patients in the General Hospital of Tianjin Medical University from February 2010 to February 2011 were enrolled. There were 34 cases of confirmed or clinically diagnosed pulmonary fungal infections, 53 cases of bacterial pneumonia, and 48 cases of non-infection diseases. All patients underwent BAL and the BALF samples were obtained. (1,3)-ß-D-glucan content (G test), in BALF and plasma were tested and the data were analyzed statistically by Mann-Whitney while the receiver operating characteristic curve (ROC curve) was established, from which the best threshold of the 2 G tests was derived. RESULTS: The median of BALF G test in the fungal infection group, pneumonia group and non-infection group was 281, 28 and 10 ng/L, respectively; the level in the fungal infection group being significantly higher than those of the other 2 groups (P < 0.001), but no significant difference being observed between the pneumonia group and the non-infection group (P > 0.05). The median of plasma G tests in the fungal infection group, the pneumonia group and the non-infection group was 27, 10, and 5 ng/L, respectively; the level in the fungal infection group being significantly higher than those in the other 2 groups (P < 0.001), but there was no significant difference between the pneumonia group and the non-infection group (P > 0.05). The best threshold of BALF G test was 67 ng/L, while the best threshold of G test of plasma was 17 ng/L. CONCLUSION: As compared to G test of plasma, G test of BALF may be more accurate, and have a higher clinical value for the earlier diagnosis of pulmonary fungal infections.

[Hepatic injury in rats exposed to chronic intermittent hypoxia and the effect of tempol].

OBJECTIVE: To investigate the mechanism of liver injury in rats exposed to chronic intermittent hypoxia (CIH) and to investigate the effect of tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl or 4-hydroxy-TEMPO). METHODS: A CIH animal model of rats was established to mimic the intermittent hypoxia/re-oxygenation (IH/ROX) of obstructive sleep apnea syndrome in humans. Thirty-two healthy male Wistar rats were randomly assigned to 4 groups: conventional intermittent hypoxia group (CIH group), intermittent hypoxia Tempol treatment group (CIH + T group), intermittent hypoxia normal saline matched group (CIH + NS group), and normoxic control group (NC group), with 8 rats in each group. The frequency of every CIH group was 30 times/h, and the minimum oxygen concentration was 5%. After the experiment, sections of liver were stained with hematoxylin-eosin (HE) and the levels of nuclear factor-kappaB (NF-κB), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) in rat liver homogenate were measured. RESULTS: Liver histology revealed that the CIH group and the CIH + NS group showed hepatocellular swelling with rarefaction of the cytoplasm, hyperchromatosis and hepatocellular membrane disruption, but the liver histology of the CIH + T group and the NC group was normal. Compared with the NC group, the levels of NF-κB and MDA in the CIH group [(12.4 ± 2.0) ng/g, (101 ± 22) µmol/g] and the CIH + NS group [(12.2 ± 1.9) ng/g, (99 ± 18)µmol/g] were increased (all P < 0.05), but the activities of GSH-PX [(88 ± 17) U/mg, (90 ± 15) U/mg] were decreased (all P < 0.05). Compared with the CIH + NS group and the CIH group, the activity of GSH-PX in the CIH + T group [(181 ± 29) U/mg] was increased (P < 0.05), but the levels of NF-κB [(7.8 ± 1.3) ng/g] and MDA [(59 ± 10) µmol/g] were decreased (all P < 0.05). The levels of GSH-PX and MDA in the CIH + T group were not significantly different compared to the NC group (P were 0.242, 0.177 respectively), but the level of NF-κB in the CIH + T group was higher than that in the NC group (P < 0.05). The levels of NF-κB, GSH-PX, and MDA in the CIH + NS group were not significantly different as compared to those in the CIH group (all P > 0.05). The level of NF-κB was correlated negatively with GSH-PX, but positively with MDA (r = -0.754, 0.689, respectively, all P < 0.01) CONCLUSIONS: CIH could cause rat liver injury through oxidative stress and activating the proinflammatory transcription factors of NF-κB. Tempol could prevent CIH-induced liver injury through scavenging ROS by its anti-oxidative effect.

[The effect of intermittent hypoxia with different degrees and frequencies on levels of superoxide dismutases and malondialdehyde in vascular endothelial cells].

OBJECTIVE: To investigate the effect of degree and frequency of intermittent hypoxia on level of superoxide dismutase (SOD) and malondialdehyde (MDA) in vascular endothelial cell. METHODS: We used umbilical vein endothelial cell ECV304 to set up cell model. The experiment cell strains contained one control group and eight experimental groups. We exposed cells by 3 different degree and 5 different frequency intermittent hypoxia gas separately as experimental groups, and the cells exposed to normal air as a control group. We determined levels of SOD and MDA by the way of ELISA in cytoblastema. RESULTS: The level of MDA of three different degree intermittent hypoxia groups were higher than the level in the control group (P < 0.01). The level of SOD in three different degree hypoxia groups is lower than the level in the group (P < 0.01). The level of SOD was decreased and the level of MDA was increased gradually with the decreasing of hypoxia degree (P < 0.01). There is a trend as the level of MDA and SOD increased and decreased with frequency decreased. The level of MDA was no different between the group of frequency in 40 per hour and 20 per hour (P > 0.05). When hypoxia frequency decreased, the level of MDA increased, and the level of 9.2 per hour exposure group was the lowest, but the level of MDA decreased again when the frequency was reaching 6.3 per hour (P < 0.01). When hypoxia frequency decreased, the level of SOD decreased, and the level of 9.2 per hour group was the highest, but the level of SOD decreased again if the hypoxia frequency was reaching 6.3 per hour (P < 0.01). The level of SOD was negative correlated to that of MDA under different hypoxia degree exposure (r = 0.932, P = 0.000), and the level of SOD was negative correlated to that of MDA under different frequency exposure (r = 0.832, P = 0.000). CONCLUSION: The intermittent hypoxia activates oxidative stress reaction in endothelial cells, and that induces the increasing of reactive oxygen species, and the antioxygen capacity become weaker. The decreasing and increasing of oxidative stress reaction depends on the degree of hypoxia and, is correlated to the frequency of hypoxia. Exposed to intermittent hypoxia, the balance of oxidative stress reaction and antioxygenative system of endothelial cell was disturbed.

Silenced lncRNA H19 and up-regulated microRNA-129 accelerates viability and restrains apoptosis of PC12 cells induced by Aß25-35 in a cellular model of Alzheimer's disease.

Accumulating data manifest that long non-coding RNA (lncRNAs) are involved in all kinds of neurodegenerative disorders, consisting of the onset and progression of Alzheimer's disease (AD). The study was for the research of the mechanism of lncRNA H19 (H19) in viability and apoptosis of PC12 cells induced by Aß25-35 in a cellular model of AD with the regulation of microRNA (miR)-129 and high mobility group box-1 protein (HMGB1). An AD cellular model of PC12 cells was established using Aß25-35. The Aß25-35-induced PC12 cells were transfected with si-H19 or miR-129 mimic to figure their roles in cell viability,apoptosis, mitochondrial membrane potential dysfunction and oxidative stress in AD. Luciferase reporter assay and RNA-pull down assay were employed for verification of the binding relationship between H19 and miR-129 and the targeting relationship between miR-129 and HMGB1. An AD mouse model was induced and brain tissues were collected. H19, miR-129 and HMGB1 were detected in Aß25-35-treated cells and brain tissues of AD mice. Elevated H19, HMGB1 and decreased miR-129 were found in Aß25-35-treated PC12 cells as well as in brain tissues of AD mice. Silenced H19 or elevated miR-129 promoted viability, inhibited apoptosis, prevented mitochondrial membrane potential dysfunction and decreased oxidative stress in Aß25-35-treated PC12 cells. H19 could specifically bind to miR-129. MiR-129 specifically suppressed HMGB1 expression. This study suggests that silenced H19 and up-regulated miR-129 accelerates viability and represses apoptosis of PC12 cells stimulated by Aß25-35 in AD, which is beneficial for AD treatment.

LncRNA NEAT1 promotes Alzheimer's disease by down regulating micro-27a-3p.

OBJECTIVE: Alzheimer's disease (AD) is a common neurodegenerative disease. This study was designed to investigate the roles of lncRNA NEAT1/miR-27a-3p axis in AD. METHODS: Amyloid protein was used to treat SH-SY5Y cells and rats to construct AD model. RT-qPCR was used to quantify lncRNA NEAT1 and micro-27a-3p in AD model cells. Western blot was used to determine the ß-amyloid-precursor-protein-cleaver-enzyme 1 (BACE1), amyloid, Tau protein and its phosphorylation, Caspase 3 protein and its lytic cell protein and amyloid precursor protein (APP). Flow cytometry was used to detect apoptosis. The cell activity was detected by CCK-8. The lncRNA NEAT1 and miR-27a-3p inhibition or over-expression vectors were constructed. The dual luciferase reporter gene and RNA pull-down assay were used to detect the targeting relationship between lncRNA NEAT1 and micro-27a-3p. The cognitive function of rats was tested by water maze. RESULTS: After being induced by amyloid protein, lncRNA NEAT1 was up-regulated while micro-27a-3p was down-regulated in SH-SY5Y cells. Apoptosis rate was increased and cell activity was decreased. Amyloid protein, BACE1 protein, APP protein, Tau protein and its phosphorylation, Caspase 3 protein and its lytic cell protein were up-regulated. Down-regulation of lncRNA NEAT1 or up-regulation of micro-27a-3p could reduce cell apoptosis, increase cell activity, down-regulate amyloid protein, BACE1 protein, APP protein, Tau protein and its phosphorylation, and up-regulate caspase 3 protein and its lysate protein. Dual luciferase reporter gene assay and RNA pull-down experiments revealed that micro-27a-3p was the target gene of lncRNA NEAT1. Down-regulation of micro-27a-3p could offset the changes caused by LncRNA NEAT1. AD caused cognitive dysfunction in rats, which was improved by down-regulation of lncRNA NEAT1. CONCLUSION: lncRNA NEAT1 regulates the development of AD by down-regulating micro-27a-3p.

Evaluating the effects of different sowing dates and tillage methods on dry-land wheat grain dry matter accumulation based on the APSIM model.

Accurate simulation of dry matter accumulation in wheat grains can provide important technical support for regulating wheat production in hilly areas of Loess Plateau. Using the APSIM model, we analyzed dryland wheat grain dry matter accumulation and distribution using the meteorological data from 1971 to 2017 in Anding District, and the field test data from 2016 to 2017 in Anjiagou Village, Fengxiang Town, Anding District, Dingxi City, Gansu Province. Furthermore, the influence of sowing date and tillage method on dry matter accumulation of wheat grain was quantitatively analyzed on the basis of model validation. The results showed that the root mean square error (RMSE) between the simulated and measured values of grain dry matter was 57.5-143.1 kg·hm-2 and the normalized root mean square error (NRMSE) was 1.4%-9.9% under the three sowing dates and four tillage methods, respectively. The precision of the APSIM model was satisfactory. Under different sowing dates, the order for beneficial degree of tillage treatment to dry matter accumulation in wheat grains was no tillage with straw cover > conventional tillage with straw cover > no tillage > conventional tillage. The treatment of no tillage with straw covered was the most favora-ble to dry matter accumulation in wheat grains, with no significant difference between no tillage and conventional tillage treatments. Under different farming methods, early sowing was better than normal sowing and late sowing for the dry matter accumulation process of wheat. Late sowing had stronger impacts on dry matter accumulation, with the least ideal accumulation process.

RETRACTED: MicroRNA-16-5p/BTG2 axis affects neurological function, autophagy and apoptosis of hippocampal neurons in Alzheimer's disease.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief as there are concerns about the reliability of the results. Concerns have been raised about the western blot bands in Figures 6 B + D having the same eyebrow shaped phenotype as found in many other publications as detailed here (https://pubpeer.com/publications/B32F93859FBAA13471ED0FFCA5BCB6). The journal requested the corresponding author to comment on these concerns and send the raw data, however the author was not able to provide uncropped images of the original gels. The Editor-in-Chief therefore no longer has confidence in the data and conclusions of this study.

Inhibition of interleukin-1ß plays a protective role in Alzheimer's disease by promoting microRNA-9-5p and downregulating targeting protein for xenopus kinesin-like protein 2.

OBJECTIVE: Evidences have indicated that interleukin-1ß (IL-1ß) and microRNAs (miRNAs) are implicated in Alzheimer's disease (AD), and we aimed to study the role of IL-1ß in AD development with the involvement of miR-9-5p and targeting protein for xenopus kinesin-like protein 2 (TPX2). METHODS: APPswe/PS1dE9 double transgenic mice and C57BL/6 wild type mice were treated with inhibited IL-1ß, miR-9-5p mimic and/or silenced TPX2. Expression of IL-1ß, miR-9-5p, TPX2, amyloid-ß (Aß) and p-tau in mouse hippocampal tissues was determined. The behavioral changes, hippocampal pathological injury, Aß plaque deposition, tau expression, neuronal apoptosis and oxidative stress of AD mice were all measured. The regulatory relationships between IL and 1ß and miR-9-5p, and between miR-9-5p and TPX2 were confirmed. RESULTS: IL-1ß and TPX2 were upregulated while miR-9-5p was downregulated in hippocampal tissues from AD mice versus non-transgenic littermate mice. Inhibited IL-1ß or elevated miR-9-5p improved behavioral changes and neuronal injury of AD mice, and suppressed plaque deposition and oxidative stress in hippocampal tissues of AD mice. These changes that induced by elevated miR-9-5p could be reversed by overexpression of TPX2. IL-1ß negatively regulated miR-9-5p, and TPX2 was a target gene of miR-9-5p. CONCLUSION: This study suggested that inhibition of IL-1ß played a protective role in AD by promoting miR-9-5p and downregulating TPX2, which may contribute to exploration on AD treatment.

Inflammation status of rabbit carotid artery model endothelium during intermittent hypoxia exposure and its relationship with leptin.

OBJECTIVES: To develop an intermittent hypoxia/reoxygenation (IH/ROX) rabbit carotid artery model and then investigate the inflammation status of rabbit carotid artery endothelium after IH exposure and its relationship with leptin. MATERIALS AND METHODS: After anesthetization, rabbit's right common carotid artery was cleared of surrounding tissue with anatomic microscope, cannulated to its distal part and the proximal part was ligated. Preparations were challenged by changing the PO(2) of the gas mixture equilibrating the perfusate. Alternate perfusing (2 mL/min) of equilibrated perfusate bubbled with normoxia or hypoxia gas mixtures formed IH/ROX cycles in the right carotid common artery, simulating the pattern of hypoxic episodes seen in obstructive sleep apnea (OSA), or continuous perfusing of hypoxia perfusate to form continuous hypoxia (CH) modes. Sixty adult male New Zealand White rabbits (2.5-3.0 kg) were separated into six groups, ten per group. Groups were: A, intermittent normoxia (IN) group, perfused with perfusion equilibrated with 21% O(2) [PO(2) about 141 +/- 2.87 mmHg] for 15 s and 21% O(2) for 1 min 45 s, 60 cycles; B, severe IH group, 5% O(2) [PO(2) about 35.2 +/- 1.27 mmHg] 15 s and 21% O(2) 1 min 45 s, 60 cycles; C, mild IH group, 10% O(2) [PO(2) about 54.3 +/- 3.31 mmHg] 15 s and 21% O(2) 1 min 45 s, 60 cycles; D, severe IH+Lep group, protocol was the same with severe IH group; E, CH group, IN for 1 h 45 min and then 5% O(2) for 15 min; and F, Lep group, the same with IN group. Right common carotid artery parts distal to the cannula were harvested after exposure, and endothelial cell layers were gotten from longitudinal outspread vessels. Nuclear factor kappaB (NFkappaB) DNA binding activities of partial cell layers were measured with electrophoretic mobility shift assay in the IN group, severe IH group, mild IH group, and CH group nuclear extracts. The other part of the cell layers in the IN group, severe IH group, severe IH+Lep group, and Lep group were cultured for 2 h, and during the culture procedure, recombinated human leptin solutions were added to culture dishes of severe IH+Lep group and Lep group (resulted concentration, 10 ng/mL). Enzyme-linked immunosorbent assay was used to analyze medium interleukin-6 (IL-6) concentrations, reverse transcription polymerase chain reaction was used to analyze endothelial cell Ras homology A (RhoA) mRNA expression levels. Statistical analysis was done with SPSS 11.5 software package. RESULTS: NFkappaB DNA binding activities were significantly different between groups (F = 112.428, P < 0.001). This activity in the severe IH group (4.27 +/- 0.64) was higher than that in the mild IH group (2.33 +/- 0.45, P < 0.001), IN group (1.00 +/- 0.26, P < 0.001), and CH group (1.15 +/- 0.36, P < 0.001). RhoA mRNA expression levels were different in groups (F = 26.634, P < 0.001).This level in the severe IH+Lep group (2.54 +/- 0.53) was higher than that in the severe IH group (1.57 +/- 0.44, P = 0.002), IN group (1.00 +/- 0.31, P < 0.001), and Lep group (1.31 +/- 0.30, P < 0.001). IL-6 concentrations were different in groups (F = 79.922, P < 0.001). IL-6 concentration in the severe IH+Lep group (1591.50 +/- 179.57 pg/mL) was higher than that in the severe IH group (1217.20 +/- 320.62 pg/mL, P = 0.036), IN group (325.40 +/- 85.26 pg/mL, P < 0.001), and Lep group (517.40 +/- 183.09 pg/mL, P < 0.001). CONCLUSIONS: IH/ROX activated the inflammation pathway significantly in the endothelium, which was more intensive than CH and intensity-dependent. When exposed to both IH/ROX and leptin, inflammation occurs more dramatically. It means that synergic activating roles were performed by IH/ROX and leptin. This study may have a clinical implication that IH can cause endothelial damage through activated inflammation in OSA patients, and if the OSA patients have obesity at the same time, the endothelial damage or the inflammation would be more significant because of elevated leptin level as a synergic factor.

Endothelial function and T-lymphocyte subsets in patients with overlap syndrome of chronic obstructive pulmonary disease and obstructive sleep apnea.

BACKGROUND: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is termed overlap syndrome (OS). COPD and OSA both have increased risks of developing cardiovascular diseases. This study aimed to explore if patients with OS exhibited a higher prevalence of cardiovascular complications, and if patients with OS exhibited vascular endothelial dysfunction and abnormalities in the cellular immune function of T lymphocytes. METHODS: Totally 25 patients with stable COPD (COPD group), 25 patients with OSA (OSA group), 25 patients with OS (OS group), and 20 healthy adults (control group) were enrolled between January 2017 and December 2017 from the Respiratory Department of Tianjin Medical University General Hospital. The clinical characteristics of the four groups were collected and the expression levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), tumor necrosis factor-α (TNF-α), and T-lymphocyte subsets were detected. One-way analysis of variance, χ test and Pearson correlation were used to manage the data. RESULTS: The prevalence of hypertension and coronary heart disease was significantly higher in the OS group than in the control, OSA, and COPD groups (χ = 20.69, P < 0.05 and χ = 11.03, P < 0.05, respectively). The levels of sVCAM-1 and TNF-α were significantly higher in the OS group than in other groups (F = 127.40, P < 0.05 and F = 846.77, P < 0.05, respectively). The percentage of CD4+ lymphocytes and CD4+/CD8+ were both significantly lower in the OS group than in any other group (F = 25.40, P < 0.05 and F = 75.08, P < 0.05, respectively). There were significantly negative correlations in the levels of sVCAM-1 and TNF-α with CD4+/CD8+ lymphocytes (r = -0.77, P < 0.05 and r = -0.83, P < 0.05, respectively). CONCLUSIONS: The prevalence of hypertension and coronary heart disease was higher in patients with OS than in patients with either OSA or COPD alone. Patients with OS exhibited more severe vascular endothelial injury, stronger inflammatory response, and lower cellular immune function.

Expression of tumor necrosis factor receptor 2 in human non-small cell lung cancer and its role as a potential prognostic biomarker.

BACKGROUND: Tumor necrosis factor receptor 2 (TNFR2) promotes tumor cell proliferation, activates immunosuppressive cells, and supports immune escape. However, its role in non-small cell lung cancer (NSCLC) has not been reported. METHODS: Quantitative real-time PCR and Western blotting were used to evaluate TNFR2 in three NSCLC cell lines (A549, H1299, H1975) and normal lung epithelial cells (BEAS-2B). TNFR2 was evaluated in 71 tumor tissues and 25 adjacent normal lung tissues by immunohistochemistry and analyzed with respect to clinical parameters. RESULTS: The messenger RNA and protein levels of TNFR2 were significantly higher in A549, H1299, and H1975 cells than in BEAS-2B cells (P < 0.05) and differed significantly between NSCLC tissues and adjacent normal lung tissues by immunohistochemistry (P < 0.0001). TNFR2 is a independent prognostic factor in NSCLC. There have significantly differences in overall survival (OS) (P = 0.006) and disease-free survival (DFS) (P = 0.000) of NSCLC patients between TNFR2 low expression groups and TNFR2 high expression group. CONCLUSION: TNFR2 is expressed in human NSCLC tissues and cell lines and is related to poor prognosis. TNFR2 may represent a new auxiliary index for patients with NSCLC.

[Carotid body inflammation and carotid sinus nerve afferent activity after intermittent hypoxia exposure of various frequencies in rabbits].

OBJECTIVE: To explore the inflammatory reactions, endothelin level and carotid sinus nerve (CSN) afferent activity of carotid body (CB) after intermittent hypoxia/reoxygenation (IH/ROX) exposure of various frequencies in rabbits. METHODS: Forty-nine male adult New Zealand white rabbits (2.5-3.0 kg) were separated into 7 groups (n = 7 each). After anesthetization, the right carotid artery and CSN were cleared of surrounding tissues without touching the right CB and the left carotid region. The CSN was unenveloped to partially expose the myelin sheath, and electrodes were placed to the "single" chemoreceptor bundle of the CSN, with CSN afferent activity carefully monitored and recorded. Then the right common carotid artery was exposed, cannulated to distal part and its proximal part was ligated. Preparations were challenged by changing the PO2 of the gas mixture equilibrating the perfusate. Alternatively perfusion (2 ml/min) of equilibrated perfusate bubbled with normoxia or hypoxia gas mixtures formed IH/ROX cycles in right carotid common artery, simulating the pattern of hypoxic episodes seen in obstructive sleep apnea, or with continuously perfusing hypoxia perfusate to form continuous hypoxia (CH) modes. Groups were defined with different frequencies, and groups were: intermittent normoxia group (IN group) (21% O2, 15 s; 21% O2, 1 min 45 s), 10/hr group (5% O2, 15 s; 21% O2, 5 min 45 s), 30/hr group (5% O2, 15 s; 21% O2, 1 min 45 s), 50/hr group (5% O2, 15 s; 21% O2, 57 s), 60/hr group (5% O2, 15 s; 21% O2, 45 s) and 90/hr group (5% O2, 15 s; 21% O2, 25 s). All the above groups were exposed to 60 treatment cycles; continuous hypoxia group (CH group), IN for 1 h 45 min and then 5% O2 for 15 min. After exposure and 30 min of static placing, CSN afferent frequencies (Charge F) were recorded from chemoreceptor bundles, and the right CB was cleared of surrounding tissues and harvested. Interleukin-6 (IL-6), endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), and vascular endothelial growth factor (VEGF) concentrations of the CB lysate were measured with enzyme linked immuno sorbent assay (ELISA) kits and standardized. Data were analyzed with SPSS 12.0 software package; and after one way analysis of variance (ANOVA) for whole difference, Tamhane's T2 was used for post hoc analysis. RESULTS: IL-6, ET-1 and Charge F increased but then decreased with increasing IH frequencies (F = 25,601.39, 2390.48, 6945.84, all P values < 0.01). IL-6, ET-1 and Charge F levels in 50/hr group were the highest among groups. Charge F levels correlated significantly with IL-6 or ET-1 (with IL-6: r = 0.736, P < 0.01; with ET-1: r = 0.757, P < 0.01, respectively). IL-6, ET-1 and Charge F levels between IN group and CH group were not statistically different (all P values > 0.05). HIF-1 levels elevated gradually (F = 5241.10, P < 0.01) with increasing exposure frequencies, and the CH group had the highest value (all P values < 0.01). VEGF level in CH group was the highest in all groups (all P values < 0.01). CONCLUSIONS: After IH/ROX exposure, afferent activity of CB CSN increases, which significantly correlates with inflammation and vasomotor mechanism of CB. CB inflammation comes not from IH phases but from ROX phases. Increased CB CSN activity results in elevated SNA tension, which plays a key role in the pathogenesis of systemic hypertension. This procedure influenced by IH/ROX frequencies. CH for 15 min causes no definitely damages. However, HIF-1 and VEGF can be considered as members of adaptive pathway during IH/ROX exposure.

Pulmonary Embolism in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

OBJECTIVE: In most countries, nearly 6% of the adults are suffering from chronic obstructive pulmonary disease (COPD), which puts a huge economic burden on the society. Moreover, COPD has been considered as an independent risk factor for pulmonary embolism (PE). In this review, we summarized the existing evidence that demonstrates the associations between COPD exacerbation and PE from various aspects, including epidemiology, pathophysiological changes, risk factors, clinical features, management, and prognosis. DATA SOURCES: We searched the terms "chronic obstructive pulmonary disease," "pulmonary embolism," "exacerbations," and "thromboembolic" in PubMed database and collected the results up to April 2018. The language was limited to English. STUDY SELECTION: We thoroughly examined the titles and abstracts of all studies that met our search strategy. The data from prospective studies, meta-analyses, retrospective studies, and recent reviews were selected for preparing this review. RESULTS: The prevalence of PE in patients with COPD exacerbation varied a lot among different studies, mainly due to the variations in race, sample size, study design, research setting, and enrollment criteria. Overall, whites and African Americans showed significantly higher prevalence of PE than Asian people, and the hospitalized patients showed higher prevalence of PE compared to those who were evaluated in emergency department. PE is easily overlooked in patients with COPD exacerbation due to the similar clinical symptoms. However, several factors have been identified to contribute to the increased risk of PE during COPD exacerbation. Obesity and lower limb asymmetry were described as independent predictors for PE. Moreover, due to the high risk of PE, thromboprophylaxis has been used as an important treatment for hospitalized patients with COPD exacerbation. CONCLUSIONS: According to the previous studies, COPD patients with PE experienced an increased risk of death and prolonged length of hospital stay. Therefore, the thromboembolic risk in patients with acute exacerbation of COPD, especially in the hospitalized patients, should carefully be evaluated.

[The relationship between arousal and nocturnal heart rate variability in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the relationship between arousal and nocturnal heart rate variability (HRV) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Twenty-seven patients with moderate to severe OSAHS who underwent overnight polysomnography (PSG) were enrolled, excluding patients with cardiopulmonary and nervous system diseases. An hour continuous PSG monitoring in non-rapid eye movement (NREM) was recorded for all patients. The mean heart rate (HR) in 10 s before each arousal and the peak HR in 10 s after arousal were compared, and the breathing disorder related arousal index (B-ArI) and pulse rate rise index (PRRI) were calculated at this time, and then a correlation analysis was performed. Furthermore, according to minimal oxygen saturation (minSaO(2)), 18 patients with moderate-to-severe OSAHS were matched into 10 events with and without EEG arousal in NREM, and then DeltaHR at apnea termination between these events were compared. RESULTS: The peak HR in 10 s after arousal onset [(81.6 +/- 9.4) beats/min] was significantly higher than the mean HR in 10 s before arousal onset [(69.6 +/- 7.3) beats/min, t = -14.87, P < 0.01], and B-ArI was positively correlated to PRRI (r = 0.97, P < 0.01). The DeltaHR of events with EEG arousal at apnea termination [(11.1 +/- 2.8) beats/min] was higher than those without EEG arousal [(7.0 +/- 2.4) beats/min, t = 4.702, P < 0.01]. CONCLUSIONS: The results indicate that arousal can influence the function of cardiovascular regulation. Frequent arousal is one of the main causes of the cardiovascular consequences in OSAHS patients.

[Changes of angiotensin II and its receptor during the development of chronic intermittent hypoxia-induced hypertension in rats].

OBJECTIVE: To observe the changes of angiotensin II (ATII) and ATII type-1 receptor (AT1R) during the development of chronic intermittent hypoxia (CIHO)-induced hypertension in rats, and the effect in the mechanism of CIHO-induced hypertension. METHODS: Seventy-two male Wistar rats were divided into three groups:intermittent hypoxia group (IH), sham control group (SC) and control group (UC). By using supply of nitrogen (30 s each cycle) followed by compressed air (30 s each cycle) into the exposure chambers (4% - 6% nadir ambient oxygen with return to 21%), IH rats were subjected to intermittent hypoxia every 60 s for 8 h/d during the diurnal sleep period. SC rats were similarly treated but received compressed air instead of nitrogen. UC rats were not treated. Mean arterial pressure (MAP), the levels of ATII and renin activity (RA) in plasma as well as the expression of AT1R mRNA in tissue were measured on day 7, 21 and 42 after experiment. RESULTS: MAP was significantly elevated in IH rats [(102.2 +/- 6.2) mm Hg, 1 mm Hg = 0.133 kPa] compared with initial MAP [(94.1 +/- 4.3) mm Hg, P < 0.01] and compared with that in SC [(95.7 +/- 3.6) mm Hg], UC [(97.2 +/- 3.6) mm Hg, all P < 0.05] on day 42. The levels of ATII and RA in plasma in IH rats increased gradually over time, and RA started to increase significantly on day 7 [(3.86 +/- 1.25) ng.ml(-1).h(-1)] compared with that in SC [(2.73 +/- 0.98) ng.ml(-1).h(-1)], UC [(2.55 +/- 0.87) ng.ml(-1).h(-1), all P < 0.05], and ATII started to increase significantly on day 21 [(214 +/- 41) ng/L] compared with that in SC [(124 +/- 21) ng/L], UC [(121 +/- 18) ng/L, all P < 0.01]. The RA and ATII levels in plasma showed positive correlation with MAP (r = 0.529, P = 0.008; r = 0.475, P = 0.019 respectively). The expression of AT1R mRNA in heart, kidney and aorta in IH rats showed no differences compared with that in SC and UC group (all P > 0.05). All indices were not different between SC and UC rats at any time point (all P > 0.05). CONCLUSION: CIHO can cause the levels of circulating RA and ATII to increase, but has no effects on AT1R mRNA expression in tissue, which suggests that activated renin-angiotensin system may contribute to the pathogenesis of CIHO-induced hypertension.