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Objective:A two-sample Mendelian randomized study was used to investigate the relationship between psychiatric disorders and the risk of developing obstructive sleep apnea(OSA).Methods:Genetic variations in bipolar disorder, depression, Alzheimer's disease and schizophrenia were used as instrumental variables and data from genome-wide association studies of OSA patients from the Finngen Consortium were used.In this study, inverse variance weighted method was used as the main analysis method, and three sensitivity analyses including weighted median analysis, MR-Egger regression analysis and MR-PRESSO analysis were jointly applied.Results:Higher genetic predisposition for depression and bipolar disorder increased the risk of developing OSA, the odds ratio is 1.18(95% CI: 1.02-1.37, P=0.026)and 1.06(95% CI: 1.01-1.12, P=0.038)for each unit increase with log-transformed odds ratios of depression and bipolar disorder, respectively.Genetic susceptibility to Alzheimer's disease and schizophrenia was not associated with the risk of developing OSA. Conclusions:This study suggests that a higher genetic predisposition for depression and bipolar disorder may lead to a higher risk of developing OSA.OSA and psychiatric disorders such as depression and bipolar disorder have a high incidence in the elderly, however, their causal effects still need to be studied.
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The main treatment methods of macular edema (ME) are intravitreal injection of anti-vacular endothelial growth factor drugs, corticosteroids, retinal laser photocoagulation and pars plana vitrectomy (PPV). However, recurrent ME, epiretinal membrane formation and drug resistance have occurred to a part of patients, which is called refractory ME (RME). PPV with internal limiting membrane peeling (ILMP) has the potential of treating and relieving RME. PPV combined with ILMP can treat and relieve RME by removing the posterior vitreous cortex, or removing the epiretinal membrane or internal limiting membrane at the same time during surgery to relieve the traction between the vitreous body and the retina. However, due to the complex pathogenesis of ME, the therapeutic effects of PPV combined with ILMP on ME caused by different etiologies still need clinical studies to explore the best surgical methods for ME caused by different etiologies.
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Objective To monitor reactive oxygen species(ROS) levels in renal proximal tubular epithelial cells cultured in vitro under albumin overload and their effect on autophagy activation,and to investigate the underlying mechanisms.Methods HK-2 cells cultured in vitro were divided into a normal control group (NC),an albumin (ALB) group,an ALB + N-acetyl-L-cysteine (NAC) group,an NAC group,an ALB+chloroquine(CQ)group and an ALB+ rapamycin(RAP)group.The expression of molecular markers for autophagy,Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3),were detected by Western blotting.ROS levels were measured by a dichloro-dihydro-fluorescein diacetate(DCFH-DA) immunofluorescence method.Results Albumin overload-induced autophagy was activated in HK-2 cells as assessed by the significant upregulation of Beclin-1 and LC3-Ⅱ levels,compared with the control group(both P＜0.05).Albumin overload triggered oxidative stress in HK-2 cells as revealed by the increased production of ROS and the enhancement of green fluorescence brightness,compared with the control group [(22.47 ± 0.79) vs.(10.15 ± 0.57),P ＜ 0.05].The antioxidant NAC significantly inhibited albumin-induced autophagy(P ＜0.05).Moreover,the increase in ROS levels caused by albumin overload was promoted by chloroquine and blocked by rapamycin (both P＜0.05).Conclusions The mechanisms for albumin overload-induced autophagy in HK-2 cells were related to oxidative stress.
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Objective To explore the relationship between obstructive sleep apnea syndrome (OSA)and sarcopenia in elderly.Methods In the retrospective analysis,totally 320 elderly patients aged 65-85 years were successively enrolled from Department of Geriatrics,General Hospital of Tianjin Medical University from January 2015 to December 2017,and divided into the sarcopenia group (n=110) and the control group (n =210).Clinical and diagnostic data of OSA and sarcopenia were collected.The correlation between OSA and sarcopenia was evaluated by using multivariate Logistic regression.Results The average age was higher in the sarcopenia group than in the control group (P ＜ 0.001).Compared with the control group,the sarcopenia group had higher proportions of patients with male (P=0.015),with obesity,type 9 diabetes,dementia or OSA (P=0.005,0.021,0.032 and 0.018,respectively).Multivariate Logistic regression showed that risk factors for sarcopenia were age≥74.3 years (OR=1.63,95％CI:1.03～2.61),male (OR=1.79,95％CI:1.13 ～2.85),obesity (OR=1.70,95％CI:1.01～ 2.90),type 2 diabetes (OR=1.91,95％CI:1.11～3.29),dementia (OR=1.92,95％CI:1.05～3.49) and OSA (OR=2.24,95％CI:1.15～4.40)(P ＜0.001,0.015,0.038,0.021,0.032 and 0.018,respectively).OSA patients is more prone to sarcopenia than patients without OSA (OR =2,24,95 ％ CI:1.15 ～ 4.40).Conclusions OSA is correlated with sarcopenia in the elderly.
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Objective: To establish a method for the determination of the particle size of nifedipine and study the effect of particle size on the in vitro dissolution behaviors of nifedipine sustained release tablets. Methods: Light scattering was used to study the parti-cle size of nifedipine API. Nifedipine APIs with different particle sizes were prepared by a portable high-speed grinder. The in vitro dis-solution curve of nifedipine sustained released tablets (Ⅰ) was determined by HPLC. The similarity was evaluated using the similarity factor ( f2) with the original drug (trade name: Adalat-L, specification: 10mg) as the reference preparation. Results: The granulo-metric conditions were as follows: the pump speed of laser size analyzer was 1 800 r·min-1, the shading rate was 8%-20% , the bal-ance time was 0 s, the media was 0. 3% Tween 80, and the ultrasonic time was 1 min. The in vitro dissolution of nifedipine sustained released tablets (Ⅰ) showed that the smaller particle size of nifedipine API, the better the dissolution was. As the Dv90 ( the particle size accounting for 90% of the total particle quantity) was reduced from 118. 781 μm to 3. 471 μm, the cumulative dissolution in 0. 25 h of nifedipine sustained released tablets (Ⅰ) increased from 11. 2% to 44. 0% , the similarity factor ( f2) compared with the dis-solution cruve of the original drug increased firstly and then decreased, and f2value was 77 when the Dv90 was 29. 823 μm. Conclu-sion: The in vitro dissolution of nifedipine sustained released tablets is improved remarkably by micronization technology. In order to produce nifedipine sustained released tablets (Ⅰ) with the same bioavailability as the original drug preparation, the particle size of nife-dipine API should be controlled within the range of 15 μm≤Dv90≤45 μm.
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Objective To evaluate changes in brain natriuretic peptide(BNP)levels in predicting the risk of acute decompensated heart failure(ADHF)in rehospitalized elderly patients.Methods A cohort study was performed in 48 elderly(≥65 years)patients hospitalized for ADHF from June 2015 to June 2016.All patients underwent standard treatment in internal medicine and were followed up for one month after discharge.The study endpoint was rehospitalization for ADHF.According to whether there was an increase in BNP levels in one-month follow-up,participants were divided into two groups:a group with increased BNP (n =20) and a group without increased BNP (n =28).General clinical information,disease history,signs of circulatory congestion,cardiac ultrasound,and BNP levels were collected and compared between the two groups.Results Compared with the group without increased BNP,the group with increased BNP had higher rates of type 2 diabetes,positive hepatoj ugular reflu x,and jugular vein engorgement (x 2 =5.749,7.243,4.286,respectively,P ＜0.05 or P ＜0.01)and lower left ventricular ejection fraction(t =-3.558,P ＜0.01).BNP increase in the BNP group was higher than in the non-BNP group(394.2 ± 171.3 ng/L vs.94.2 ± 56.3 ng/L,P ＜0.01).The rehospitalizationrate in the BNP group was significantly higher than in the non-BNP group(55 ％ or 11 patients vs.17.8％ or 5 patients,P＜0.01).Multivariate Cox regression analysis found that the increase in BNP in the one-month follow-up was correlated with the increase in rehospitalization(HR =4.118,95％CI:1.427-11.884,P＜0.01).When the absolute value of BNP rose to over 310ng/L,the risk of rehospitalization in ADHF patients increased.Conclusions Increase in BNP one month after discharges is an effective predictor for rehospitalization in elderly patients with ADHF.
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Objective To investigated the effects of intermittent hypoxia on neuronal apoptosis and autophagy in hippocampus.Methods 30 Wistar rats were randomly divided into normal control group (NC),intermittent normoxia group (IN) and intermittent hypoxia group (IH).The spatial learning and memory function of the rat was assessed using Morris water maze test.The apoptotic cells and the ultrastructure of neurons in the hippocampus tissue were observed by TUNEL and transmission electron microscope,respectively.And the expression of autophagy marker protein LC3 and Beclin-1 were measured by Western blotting.Results The escape latency was significantly longer in IH than in NC and IN group.And the ratio of time spent in the target quadrant was lower in the IH group than in NC and IN group (P＜0.05).The apoptotic rate of rat hippocampal neurons (F =6.01,P=0.037),the amount of double-layer membrane structure-complicating autophagic vacuoles with karyopyknosis,and protein expression level of LC3 and Beclin-1 were significantly higher (all P ＜0.05) in intermittent hypoxia group than in IN and NC group.Conclusions Intermittent hypoxiainduced autophagy and apoptosis in rat hippocampus are significantly increased,which might be one of the possible mechanisms for cognitive dysfunction caused by intermittent hypoxia.
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Objective To investigate the effect of chronic intermittent hypoxia on blood pressure,sympathetic nerve activity and myocardial mitochondrial oxidative stress status in aged rats.Methods Chronic intermittent hypoxia(CIH)rat models were established.A total of 84 male Wistar rats(3-4 and 23-24 months old,respectively)were randomly and equally divided into four groups according to age:young control group,young CIH group,aged control group and aged CIH group.CIH exposure lasted for 3 weeks.The arterial blood pressure,the frequency of carotid sinus nerve action potential,the lung function,the levels of catecholamine,aconitase/fumarate ratio (A/F),plasma superoxide dismutase(SOD)in the plasma were measured and compared between four groups.Results The arterial blood pressure was significantly higher in young CIH group than in the young control group[(150.4 ±25.6)mmHg vs.(102.2±7.4)mmHg,P＜0.01].There was no significant difference in the arterial blood pressure between the aged CIH group[(132.8 ±16.2) mmHg] and the aged control group[(127.1 ± 26.8)mmHg].The minute volume ventilation was significantly lower in the aged control group than in young controlgroup[(331.7±53.5)ml· min-1 · kg-1vs.(554.8±111.9)ml· min-1 · kg-1P＜0.05].The min-1 · kg-1 ventilation showed no significant difference between the agedCIH group[(354.1±51.9)ml· min-1 · kg-1]and the aged control group[(331.7 ±53.5)ml· min-1 · kg-1].The rate of CSN frequency change by hypoxia stimulation was lower in the aged control group than in young control group[(6.2± 5.5)times vs.(11.8 ±6.6)times,P＜0.01],and was lower in the aged CIH group than in the young CIH group[(22.2 ± 13.5) times vs.(44.2± 12.1) times,P＜0.01].The levels of plasma norepinephrine and epinephrine were higher in the young CIH group than in the control group[(39.0±8.9)nmol/L vs.(20.8±10.6)nmol/L,(48.1±13.6)nmol/L vs.(26.7 ± 14.3)nmol/L,both P＜0.05].The levels of plasma norepinephrine and epinephrine showed no significant difference between the aged control group and the young control group,also no significant difference was found between the aged CIH group and the aged control group.The A/F ratio was lower in the young CIH group than in the young control group[(0.26±0.13)vs.(0.58 ±0.04),P＜0.01].The A/F ratio was lower in the aged control group than in the young control group [(0.29±0.02)vs.(0.58± 0.04),P＜0.01],but there was no significant difference in the A/F ratio between the aged CIH group and the aged control group.The level of SOD was significantly lower in the young CIH group than in the young control group [(5.30 ±± 0.90) NU/mgprot vs.(6.10 ± 1.73)NU/mgprot,P＜0.05].There was no significant difference in SOD level between aged control group and aged CIH group.Conclusions The effect of CIH on blood pressure in aged rats is different from the youth rats.This study shows adecreasedsympathetic nervous over activity and a reducedmitochondrial oxidative stress in aged rats.Aging probably suppresses two important pathogenic mechanisms,by which CIH affects blood pressure,therefore releases CIH induced blood pressure abnormality.