Influenza A virus exposure may cause increased symptom severity and deaths in coronavirus disease 2019 / 中华医学杂志(英文版)

BACKGROUND@#The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19.@*METHODS@#Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups.@*RESULTS@#Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir.@*CONCLUSIONS@#The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.

Implementing antimicrobial management toimprove susceptibility of Pseudom onas aeruginosa to carbapenems / 中国感染控制杂志

Objective To analyze susceptibility of clinically isolated Pseudomonas aeruginosa(PA)to carbape-nems,and observe the effect of classified management of antimicrobial agents on carbapenem susceptibility.Methods PA isolated from Peking University Cancer Hospital between October 2012 and March 2014 were collected,uni-variate analysis and multivariate logistic regression analysis were adopted to study the risk factors for non-suscepti-bility to carbapenems,susceptibility of PA to carbapenems before and after the implementation of classified manage-ment of antimicrobial agents was analyzed.Results A total of 125 strains of PA were isolated,mainly from patients with esophageal cancer(n=30,24.0%)and colorectal cancer(n=29,23.2%);the main specimens were drainage fluid and wound secretion(n=62,49.6%);the main source departments were surgical wards(n=86,68.8%). Univariate analysis showed that non-susceptibility of PA to carbapenems was related to strains from surgical wards,hospitalization within 3 months,carbapenem exposure,and length of hospital stay>4 weeks. Logistic regression analysis showed that 3 independent risk factors were:strains from surgical wards,exposure to carbapenems,and length of hospital stay>4 weeks. Susceptibility of PA to carbapenems after implementation of antimicrobial man-agement was 74.6%,which was higher than 53.4% before management(P= 0.015).Conclusion Strains from surgical wards,carbapenem exposure,and length of hospital stay>4 weeks are independent risk factors for no-sus-ceptibility of PA to carbapenems;susceptibility of PA to carbapenems is increased after strict implementation of antimicrobial classified management system.

Relationship between Radiological Stages and Prognoses of Pneumocystis Pneumonia in Non-AIDS Immunocompromised Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although radiological features of pneumocystis pneumonia (PCP) in non-Acquired Immune Deficiency Syndrome (AIDS) immunocompromised patients have been reported by other authors, there were no studies on the radiological stages of PCP previously. This study aimed to elucidate the radiological stages and prognoses of PCP in non-AIDS immunocompromised patients.</p><p><b>METHODS</b>Retrospective analysis of radiological manifestations and prognoses of 105 non-AIDS PCP immunocompromised patients from August 2009 to April 2016 was conducted. Chest radiograph was divided into three stages: early stage (normal or nearly normal chest radiograph), mid stage (bilateral pulmonary infiltrates), and late stage (bilateral pulmonary consolidations); chest high-resolution computed tomography (HRCT) was also divided into three stages: early stage (bilateral diffuse ground-glass opacity [GGO]), mid stage (bilateral diffuse GGO and patchy consolidations), and late stage (bilateral diffuse consolidations).</p><p><b>RESULTS</b>The case fatality rate (CFR) of all patients was 34.3% (36/105), all of them took routine chest X-ray (CXR), and 84 underwent chest CT examinations. According to the CXR most near the beginning of anti-PCP therapy, 18 cases were at early stage and CFR was 0 (0/18, P< 0.01), 50 cases were at mid stage and CFR was 28.0% (14/50, P> 0.05), and 37 cases were at late stage and CFR was 59.5% (22/37, P< 0.01). According to the chest HRCT most near the beginning of anti-PCP therapy, 40 cases were at early stage and CFR was 20.0% (8/40, P> 0.05), 34 cases were at mid stage and CFR was 47.1% (16/34, P> 0.05), and 10 cases were at late stage and CFR was 80.0% (8/10, P< 0.05); barotrauma, including pneumothorax, pneumomediastinum, and pneumohypoderma, was found in 18 cases and the CFR was 77.8% (14/18, P< 0.01).</p><p><b>CONCLUSIONS</b>Based on the radiological manifestations, the course of PCP in non-AIDS immunocompromised patients can be divided into three stages: early stage, mid stage, and late stage. The prognoses of patients treated at early stage are good, and those at late stage are poor. Furthermore, the CFR of patients with barotrauma is high.</p>

Living near a Major Road in Beijing: Association with Lower Lung Function, Airway Acidification, and Chronic Cough / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effects of near-road pollution on lung function in China have not been well studied. We aimed to investigate the effects of long-term exposure to traffic-related air pollution on lung function, airway inflammation, and respiratory symptoms.</p><p><b>METHODS</b>We enrolled 1003 residents aged 57.96 ± 8.99 years living in the Shichahai Community in Beijing. Distances between home addresses and the nearest major roads were measured to calculate home-road distance. We used the distance categories 1, 2, and 3, representing <100 m, 100-200 m, and >200 m, respectively, as the dose indicator for traffic-related air pollution exposure. Lung function, exhaled breath condensate (EBC) pH, and interleukin 6 levels were measured. As a follow-up, 398 participants had a second lung function assessment about 3 years later, and lung function decline was also examined as an outcome. We used regression analysis to assess the impacts of home-road distance on lung function and respiratory symptoms. As the EBC biomarker data were not normally distributed, we performed correlation analysis between home-road distance categories and EBC biomarkers.</p><p><b>RESULTS</b>Participants living a shorter distance from major roads had lower percentage of predicted value of forced expiratory volume in 1 s (FEV1% -1.54, 95% confidence interval [CI]: -0.20 to -2.89). The odds ratio for chronic cough was 2.54 (95% CI: 1.57-4.10) for category 1 and 1.97 (95% CI: 1.16-3.37) for category 2, compared with category 3. EBC pH was positively correlated with road distance (rank correlation coefficient of Spearman [rs] = 0.176, P < 0.001).</p><p><b>CONCLUSIONS</b>Long-term exposure to traffic-related air pollution in people who live near major roads in Beijing is associated with lower lung function, airway acidification, and a higher prevalence of chronic cough. EBC pH is a potential useful biomarker for evaluating air pollution exposure.</p>

Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Studies of interleukin (IL)-4 and IL-6 in the exhaled breath condensate (EBC) of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid (ICS) treatment on IL-4 and IL-6 in the EBC of asthmatic patients.</p><p><b>METHODS</b>In a prospective, open-label study, budesonide 200 μg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma (mean age 42.7 years) for 12 weeks. Changes in asthma scores, lung function parameters (forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEF50], forced expiratory flow at 75% of forced vital capacity, maximum mid-expiratory flow rate) and the concentrations of IL-4 and IL-6 in EBC were measured.</p><p><b>RESULTS</b>Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 ± 0.56 pmol/L before treatment to 1.60 ± 0.36 pmol/L after 8 weeks of treatment (P < 0.05) and 1.54 ± 0.81 pmol/L after 12 weeks of treatment (P < 0.01). However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEV1, PEF and FEF50 values (correlation coefficients -0.468, -0.478, and -0.426, respectively).</p><p><b>CONCLUSIONS</b>The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics.</p>

Small RNA interference-mediated ADP-ribosylation factor 6 silencing inhibits proliferation, migration and invasion of human prostate cancer PC-3 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of silencing ADP-ribosylation factor 6 (Arf6) on the proliferation, migration, and invasion of prostate cancer cell line PC-3 and the possible molecular mechanisms.</p><p><b>METHODS</b>Three Arf6-specific small interfering RNA (siRNA) were transfected into cultured prostate cancer cell line PC-3. Arf6 expression was examined by real-time PCR and Western blotting. MTT assay, wound healing assay, and Transwell migration and invasion assay were used to observe the effect of Arf6 silencing on the proliferation, migration, and invasion ability of PC-3 cells. The levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, p-AKT, AKT and Rac1 were detected by Western blotting.</p><p><b>RESULTS</b>Transfection of siRNA-3 resulted in significantly decreased Arf6 mRNA and protein expression with inhibition rates of (91.88±3.13)% and (86.37±0.57)%, respectively. Arf6 silencing by siRNA-3 markedly suppressed the proliferation, migration and invasion of PC-3 cells and reduced the expression levels of p-ERK1/2 and Rac1.</p><p><b>CONCLUSION</b>Silencing of Arf6 efficiently inhibits the proliferation, migration, and invasion of PC-3 cells in vitro, and the underlying mechanisms may involve the down-regulation of p-ERK1/2 and Rac1.</p>

Clinical Manifestations of Fibrosing Mediastinitis in Chinese Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fibrosing mediastinitis (FM) is a rare disease. FM is thought to be related to prior granulomatous mediastinal infection, such as histoplasmosis or tuberculosis. The majority of cases have been reported in endemic regions for histoplasmosis. The characteristics of cases of FM in China, where the prevalence of tuberculosis is high, have not been reported. We analyzed the clinical, imaging, and bronchoscopic features of Chinese patients with FM to promote awareness of this disease.</p><p><b>METHODS</b>Between January 2005 and June 2015, twenty patients were diagnosed with FM in our hospital. Medical records and follow-up data were collected. Imaging and biopsy findings were reviewed by radiologists and pathologists.</p><p><b>RESULTS</b>A total of 20 patients were analyzed (8 males and 12 females). The age ranged from 43 to 88 years with a mean age of 69.5 years. Previous or latent tuberculosis was found in 12 cases. Clinical symptoms included dyspnea (18/20), cough (17/20), expectoration (7/20), and recurrent pneumonia (3/20). Chest computed tomography scans showed a diffuse, homogeneous, soft tissue process throughout the mediastinum and hila with compression of bronchial and pulmonary vessels. Calcification was common (15/20). Pulmonary hypertension was present in 9 of 20 cases. Diffuse black pigmentation in the bronchial mucosa was frequently seen on bronchoscopy (12/13). The patients' response to antituberculosis treatment was inconsistent.</p><p><b>CONCLUSIONS</b>FM in Chinese patients is most likely associated with tuberculosis. Some characteristics of FM are different from cases caused by histoplasmosis.</p>

Improved methods for monitoring sleep state and respiratory rhythm in freely moving rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To improve the method for monitoring sleep state and respiratory rhythm of SD rats, providing a solution for rats' chewing on the wires, signal loss and instability problems in the animal model of sleep apnea syndrome (SAS).</p><p><b>METHODS</b>We improved monitoring electrodes of both electrocorticogram (ECoG) and electromyogram (EMG), signal circuit and animal operation.</p><p><b>RESULTS</b>Operation time was shortened and wound exposure time was reduced, which made it easier for postoperative recovery. The ECoG and EMG signals were more stable with sharp image, and signal circuit lines had better conductivity and material durability, achieving continuous monitoring for a long time and high success rate. We could precisely distinguish the sleep wake state and the sleep apnea events in rats according to these signals.</p><p><b>CONCLUSION</b>The improved method is more reliable and practical to test the small animal model of SAS, and is more easily to operate and the signals are more stable.</p>

Effects of long-term sleep deprivation on mitochondria stress in locus coeruleus and the tyrosine hydroxylasic projection in mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the changes of mitochondria stress in locus coeruleus and the tyrosine hydroxylasic projection after long-term sleep deprivation.</p><p><b>METHODS</b>Sleep deprivation mice model was set up by employing "novel environments" method. The expression of NAD -dependent deacetylase Sirtuin type 3 (SIRT3), which regulates mitochondrial energy production and oxidative stress, and heat shock protein 60 (HSP60), a major biomarker of mitochondrial stress, and the tyrosine hydroxylasic projection from locus coeruleus were analyzed after a 5-day sleep deprivation.</p><p><b>RESULTS</b>Compared to the control group, the expression of SIRT3 in locus coeruleus was significantly decreased in respouse to long-term sleep deprivation, while the expression of HSP60 was significantly increased. In addition, relative to control group, pereentage area of the tyrosine hydroxylasic projection to anterior cingulate cortex was substantial decreased in long-term sleep deprivation group.</p><p><b>CONCLUSION</b>Long-term sleep deprivation induced the decreased level of SIRT3 expression and the elevation of mitochondrial stress in locus coenileus, which may further lead to the loss of tyrosine hydroxylasic projection in mice.</p>

Elevated nocturnal and morning blood pressure in patients with obstructive sleep apnea syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The nocturnal nondipping and elevated morning blood pressure (BP) in patients with obstructive sleep apnea syndrome (OSAS) have not yet been well investigated in Chinese patients. This study aimed to describe the BP profile, and to elucidate the relationships between daytime BP and nighttime BP, and between evening BP and morning BP in patients with OSAS.</p><p><b>METHODS</b>Twenty teaching hospital sleep centers in China were organized by the Chinese Medical Association to participate in this study and 2297 patients were recruited between January 2004 and April 2006. BP assessments were made at four time points (daytime, evening, nighttime and morning) and polysomnography (PSG) was performed and subjects were classified into four groups by their apnea-hypopnea index (AHI): control, n = 213 with AHI < 5; mild, n = 420 with AHI ≥ 5 and < 15; moderate, n = 460 with AHI ≥ 15 and < 30; and severe, n = 1204 with AHI ≥ 30. SPSS 11.5 software package was used for statistical analysis and figure drawing.</p><p><b>RESULTS</b>All the average daytime, nighttime, evening and morning BPs were positively correlated with AHI and negatively correlated with nadir nocturnal oxygen saturation. The ratios of nighttime/daytime and morning/evening average BP were positively correlated with AHI. The ratio of nighttime/daytime systolic BP became a "reversed BP dipping" pattern until the classification reached severe, while the ratio of nighttime/daytime diastolic BP became reversed at moderate. Similarly, the ratio of morning/evening diastolic BP becomes reversed even at mild.</p><p><b>CONCLUSIONS</b>OSAS may result in higher BP levels at all four time points. The ratios of nighttime/daytime and morning/evening BP increase with increased AHI. The increasing of diastolic BP, which is inclined to rise more quickly, is not parallel with increasing systolic BP.</p>

The enhancing effect of Angelica dahurica extracts on absorption of baicalin--the active composition of Scutellaria / 药学学报

To explore the mechanism of the absorption enhancement of Angelica dahurica extract (Ade), the absorption mechanism of baicalin in the Scutcllaria water extraction as well as the effect of Angelica dahurica extract on absorption of baicalin were investigated. In order to determine the main absorption site, everted intestinal sac model was used to study the effect of Angelica dahurica extract on the absorption of baicalin at duodenum, jejunum, ileum and colon. In situ single pass intestinal perfusion model was performed to study the absorption of various concentrations of baicalin and the effect of Angelica dahurica extract on the absorption of baicalin at the main absorption site. To authenticate the consequence of perfusion by getting the blood from the hepatic portal vein and determine the concentration of the baicalin in the blood. The result showed that baicalin could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows: ileum > colon > jejunum > duodenum. The absorption ofbaicalin in the duodenum significantly increased with Angelica dahurica extract, thus, duodenum was chosen to be the studying site. Apparent permeability values (Papp) and absorption rate constant (Ka) of baicalin in the duodenum increased gradually with higher concentrations. When the concentration of baicalin rises to a certain degree, the absorption increase had a saturable process, the absorption of baicalin may be an active transportation. Baicalin may be not a substrate of P-gp as verapamil which had not significantly affected the Papp and Ka of baicalin. The absorption of baicalin in the duodenum significantly increased (P < 0.01) in the two models with Angelica dahurica extract and the concentration of baicalin in the blood from the hepatic portal vein showed that the Angelica dahurica extract can increase the absorption of baicalin.

A clinical comparative study of polymerase chain reaction assay for diagnosis of pneumocystis pneumonia in non-AIDS patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pneumocystis jirovecii pneumonia (PCP) is one of the most common and fatal infections in non-AIDS immunocompromised patients, which is difficult to diagnose by traditional morphologic methods. This study evaluated polymerase chain reaction (PCR) assays of Pneumocystis jirovecii mitochondrial large subunits ribosomal RNA in sputum and bronchioalveolar lavage fluid (BALF) for diagnosing PCP.</p><p><b>METHODS</b>Sputum and BALF specimens from two groups were collected: one group (PCP group) included 20 patients definitely diagnosed of PCP by Gomori methenamine silver (GMS) stains of BALF; the other group (non-PCP group) included 40 patients. Each specimen was examined by GMS stains and PCR assays.</p><p><b>RESULTS</b>GMS stains of BALF in PCP group were 100% positive (20/20), GMS stains of sputum in PCP group were 35% positive (7/20); GMS stains of BALF in non-PCP group were 100% negative (40/40), GMS stains of sputum in non-PCP group were 100% negative (40/40). PCR assays of BALF in PCP group were 100% positive (20/20), PCR assays of sputum in PCP group were 100% positive (20/20); PCR assays of BALF in non-PCP group were 100% negative (40/40), PCR assays of sputum in non-PCP group were 100% negative (40/40). Sensitivity and specificity of PCR assays of sputum and BALF were both 100%; positive and negative predictive values were also both 100%.</p><p><b>CONCLUSION</b>The diagnostic value of PCR assays of Pneumocystis jirovecii mitochondrial large subunits ribosomal RNA on sputum and BALF for pneumocystis pneumonia are both high and equivalent.</p>

Prospective study of first night effect on 2-night polysomnographic parameters in adult Chinese snorers with suspected obstructive sleep apnea hypopnea syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A prospective 2-night polysomnographic (PSG) study in Chinese snorers was designed to assess the role of the first night effect (FNE) in PSG parameters and the diagnosis of obstructive sleep apnea hypopnea syndrome (OSAHS).</p><p><b>METHODS</b>Seventy-two snorers from two teaching hospitals underwent overnight PSG on two consecutive nights. The night-to-night variability of PSG parameters were recorded and analyzed.</p><p><b>RESULTS</b>Sixty-six patients were analyzed. Among all the PSG parameters, only the total time of stage 2 presented a significant difference between two nights: 219.50 (83.50 - 353.50) vs. 215.25 (59.50 - 342.50) (P = 0.000). Subgroup assessment showed a slight night-to-night difference in about 1 - 2 parameters in the group with the apnea-hypopnea index (AHI) ≥ 20 events per hour as well as the group with AHI < 20 events per hour, but there was no night-to-night difference in the AHI in each group. And slighter FNE was found among patients ≥ 40 years old. There was no significant difference in diagnosis of OSAHS. In the decision of severity, a slight difference was found between the two nights with a Kappa value = 0.531.</p><p><b>CONCLUSIONS</b>Only mild FNE can be found on two consecutive nights of PSG in adult Chinese snorers, but it has no effect on the diagnosis of OSAHS. A single polysomnographic night may be adequate for the diagnosis of OSAHS.</p>

Naringin inhibits monocyte adhesion to high glucose-induced human umbilical vein endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of naringin on monocyte adhesion to high glucose-induced human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>Cultured HUVECs isolated from human umbilical cords were pretreated with or without naringin and induced with high glucose (33 mmol/L) for 48 h. Human monocyte THP-1 cells, after labeling with BCECF-AM, were co-cultured with the HUVECs for 30 min. The labeled THP-1 cells adhering to HUVECs were observed under fluoroscence microscope, and the inhibitory effect of naringin on the cell adhesion was evaluated by measuring the adhering cell density. Western blot analysis was used to detect the expressions of the adhesion molecules in the HUVECs, and reactive oxygen species (ROS) production in the HUVECs was measured using an oxidation-sensitive fluorescent probe (DCFH-DA). The nuclear extracts of the HUVECs were prepared to examine the expression of nuclear factor-kappa B (NF-kappaB) in the cell nuclei by Western blotting.</p><p><b>RESULTS</b>HUVECs in high-glucose culture showed increased adhesion to THP-1 cells and enhanced expressions of the cell adhesion molecules, which were significantly attenuated by pretreatment with naringin (10-50 microg/ml). High glucose induced DCF-sensitive intracellular ROS production in the HUVECs, and this effect was inhibited by naringin pretreatment of the cells. Naringin also suppressed high glucose-induced increment of NF-kappaB expression in the cell nuclei of HUVECs.</p><p><b>CONCLUSION</b>Naringin can suppress high glucose-induced vascular inflammation possibly by inhibiting ROS production and NF-kappaB activation in HUVECs.</p>

Relationship of daytime blood pressure and severity of obstructive sleep apnea among Chinese: a multi-center investigation in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epidemiologic studies have shown an independent and definite association between obstructive sleep apnea (OSA) and hypertension. This study aimed to define the association between daytime blood pressure and severity of OSA in Chinese population in mainland of China.</p><p><b>METHODS</b>Twenty university hospital sleep centers in mainland of China were invited by the Chinese Medical Association (CMA) to participate in this epidemiologic study and 2297 consecutive patients (aged 18 - 85 years; 1981 males and 316 females) referred to these twenty sleep centers for evaluation of OSA between January 2004 and April 2006 were prospectively enrolled. Nocturnal polysomnography was performed in each patient, and disease severity was assessed based on the apneahypopnea index (AHI). These patients were classfied into four groups: nonapneic control (control, n = 257) with AHI < or = 5 episodes/hour; mild sleep apnea (mild, n = 402) with AHI > 5 and < or = 15 episodes/hour; moderate sleep apnea (moderate, n = 460) with AHI > 15 and < or = 30 episodes/hour and severe sleep apnea (severe, n = 1178) with AHI > 30 episodes/hour. Daytime blood pressure measurements were performed under standardized conditions in each patient at 10 a.m. in office on the day of referring to sleep centers for getting average value. All the patients were requested to quit medications related to blood pressure for three days before the day of assessing.</p><p><b>RESULTS</b>Both daytime systolic blood pressure and diastolic blood pressure values were significantly related to AHI positively (r = 0.201 and 0.276, respectively; both P values < 0.001) and to nadir nocturnal oxygen saturation negatively (r = -0.215 and -0.277, respectively; both P values < 0.001), which were the parameters of OSA severity. In two special designed mean plots, means of daytime systolic and diastolic blood pressure increased gradually with increasing AHI. Beyond AHI of 61 - 65, this increasing trend reached a plateau.</p><p><b>CONCLUSIONS</b>The results showed that OSA severity was associated with daytime blood pressure until AHI of 61 - 65, providing evidence for early OSA management, especially in OSA patients with concomitant hypertension.</p>

Effects of 5-hydroxytryptamine and 5-hydroxytryptamine 2A/2C agonist on the genioglossus activity and sleep apnea in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>5-Hydroxytryptamine (5-HT) is a common neurotransmitter in the brain which plays an important role in the pathogenesis of sleep apnea. Dysfunction of 5-HT and 5-HT(2) receptors may lead to the collapse of the upper airway and the instability of respiratory control, which in turn produce apnea. Genioglossus (GG) is one of the most important oropharyngeal muscles maintaining the upper airway open. The present study aimed to investigate the effects of 5-HT and 5-HT(2) receptor on GG activity and the sleep apnea in Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>Microinjection probes were placed within the fourth ventricle of sixteen SD rats. After recovery for a week, the electromyogram (EMG) of GG was recorded in the anesthetized and vagotomized rats. The changes of GG activity before and after the microinjection of 5-HT or 5-HT(2A/2C) agonist -2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) were observed. Probes were also laid in another eight SD rats. Electroencephalogram (EEG), EMG of neck muscle and respiration were recorded at the same time a week later. The effects of DOI on the occurrence of sleep apnea were explored.</p><p><b>RESULTS</b>Both 5-HT and DOI significantly enhanced the activity of GG just 3 minutes after the completion of injection. The effect of 5-HT disappeared quickly and the effect of DOI lasted for more than 27 minutes. DOI also significantly decreased the post-sigh apnea index in non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep and decreased the spontaneous apnea index only in NREM sleep (P < 0.05, respectively).</p><p><b>CONCLUSION</b>5-HT and 5-HT(2A/2C) system correlated closely with the pathogenesis of the sleep apnea syndrome and 5-HT receptors may become the target of the drug treatment.</p>

Pharmacokinetics and relative bioavailability of ziprasidone tablets in Chinese healthy volunteers / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the pharmacokinetics and bioavailability of ziprasidone tablets in Chinese healthy volunteers.</p><p><b>METHODS</b>A randomized crossover study was performed in 20 healthy volunteers, who received a single oral dose (40 mg) of the test or reference preparation of ziprasidone. Blood samples were collected from the subjects at different time points following the drug administration, and the plasma concentration of ziprasidone was determined using high-performance liquid chromatography. The pharmacokinetic parameters were analyzed by DAS software and the relative bioavailability was calculated according to the formula F=AUC(t)/AUC(r)x100%.</p><p><b>RESULTS</b>For the test and reference preparation, the pharmacokinetics parameter C(max) was 170.7-/+71.3 and 174.4-/+81.6 ng/ml, t(max) 3.73-/+1.87 and 3.69-/+1.84 h, t((1/2)) 5.57-/+1.62 and 5.61-/+1.73 h, AUC(0-t) 1273-/+252.3 and 1296-/+266.9 ng.h.ml(-1), and AUC(0-infinity)1396-/+276.9 and 1407-/+281.5 ng.h.ml(-1), respectively, with the relative bioavailability of (98.3-/+12.6)%. No significant differences were found in the main parameters of the test and reference preparations as analyzed by ANOVA and two- and one-side t-test.</p><p><b>CONCLUSION</b>The test and reference preparation of ziprasidone are bioequivalent.</p>

Establishment of homogeneous time-resolved fluorescence immunoassay for high throughput screening of protein tyrosine kinase inhibitors / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish an in vitro homogeneous time-resolved fluorescence immunoassay method for high throughput screening of protein tyrosine kinase (PTK) inhibitors.</p><p><b>METHODS</b>Specific fluorescence signals at 670 and 612 nm were measured by multifunctional microplate reader when the fluorescence was emitted through a resonance energy transfer between fluorescent materials (EuK and XL-665). The inhibitory activity of Sunitinib, a standard PTK inhibitor, on vascular endothelia growth factor receptor 2 (VEGFR-2) kinase activity was investigated.</p><p><b>RESULTS</b>A homogeneous time-resolved fluorescence immunoassay was established for high throughput screening of PTK inhibitor. In this system, the concentrations of VEGFR-2, adenosine triphosphate (ATP) and poly-peptide substrate were 5 ng/microl, 100 micromol/L and 1 micromol/L, respectively. Sunitinib inhibited VEGFR-2 kinase activity with an IC50 value of 86.7 nmol/L, which was close to the values tested using other methods.</p><p><b>CONCLUSION</b>The homogeneous time-resolved fluorescence immunoassay we established can be easily used for high throughput screening of PTK inhibitors.</p>

Influence of combination of extractum Angelicae Dahuricae Siccum and total alkaloids of Rhizoma Corydalis on pharmacokinetics of tetrahydropalmatine in rats / 药学学报

This paper is aimed to develop a rapid and sensitive HPLC-fluorescence detection (FLD) method for the determination of tetrahydropalmatine (TET) in rats' plasma. The influence of combinations of Extractum Angelicae Dahuricae Siccum (coumarin and volatile oil) and total alkaloids (TA) from Rhizoma Corydalis (TA) on pharmacokinetics of TET in rats was studied. Plasma samples were treated with hexane-isopropanol (95:5) to precipitate the protein, and were determined by HPLC-fluorescence detection. The calibration curve was linear in the range of 2.096-167.68 microg L(-1). The limit of quantification was 2.096 microg L(-1). The method recovery of TET was 94.0%-100.0%. The extract recovery was 72.0%-81.5%. RSDs ofintra- and inter-day precisions were all less than 7.0%. Pharmacokinetics of TET in rats was fitted to two compartments open model after oral administration of TA, TA-volatile oil (VO), TA-coumarin (Cou) and TA-VO-Cou. Compared with TA, AUC(0-t), AUC(0-infinity), MRT(0-t), and MRT(0-infinity) of TET had significant deviation when combined with VO and/or Cou. The determination method is sensitive, specific, accurate, and appropriate for determination of TET in vivo. Coumarin and/or VO combined with TA can prolong the resistance time of TET significantly, delay elimination and enhance bioavailability of tetrahydropalmatine.

Modulation of leak K(+) channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value / 生理学报

The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.