ABSTRACT
Obstructive sleep apnea (OSA) is a common sleep disordered breathing disorder. As a major global public health problem, untreated OSA can lead to a variety of adverse health outcomes, including various cardiovascular and cerebrovascular diseases, metabolic disorders, and psychiatric disorders such as anxiety and depression. Traditional OSA therapies such as positive airway pressure (PAP), weight loss, oral appliance, upper airway surgery, and postural therapy focus on the anatomical factors of OSA. However, the pathogenesis of OSA is heterogeneous, and non-anatomical factors also play an important role in most patients. Although there is no drug with exact efficacy for the treatment of OSA, with the deepening understanding of the pathophysiological mechanism of OSA, more and more clinical studies are devoted to the study of drug treatment of OSA and its complications, and a series of results have been achieved. The following is a review of the relevant studies on drug treatment of OSA in recent years, hoping to provide literature support and theoretical basis for future research on drug treatment of OSA.
ABSTRACT
Mammalian cell defense mechanisms are constantly evolving in response to increasing endogenous and exogenous oxidative stress factors. In recent years, as research has deepened, nuclear factor E2-related factor 2 (Nrf2) has been hailed as a "star" molecule in antioxidant damage defense. Billions of dollars have been spent internationally on developing targeted activators or inhibitors. Obstructive sleep apnea (OSA) is the most common form of sleep breathing disorder in clinical practice. Oxidative stress is one of its main pathological mechanisms and is closely related to target organ damage in the heart, brain, lungs, kidneys, and other systems. Recent research has revealed the mechanistic relationship of the Nrf2 pathway in OSA complications, and some natural Nrf2 activators have demonstrated emerging therapeutic effects in animal experiments. However, the activation mode and effect pathway of Nrf2 in different target organs of OSA have not been clarified. Therefore, this article reviews the research progress of the Nrf2 pathway in OSA and its complications, to deepen understanding of the mechanism of OSA complications and provide a potential treatment strategy.
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal chronic interstitial lung disease characterized by a progressive decline in lung function, and current treatment options are limited. cAMP is one of the most important second messengers and plays a key role in relaxing airway smooth muscle cells and reducing inflammation. Phosphodiesterase (PDE) is a superfamily of enzymes, and PDE4 enzymes dominate 11 PDE superfamily enzymes, available in four isoforms-PDE4A, PDE4B, PDE4C and PDE4D, which selectively decompose cAMP, while PDE4 inhibitors increase cAMP levels by preventing cAMP from breaking down, thereby exerting anti-inflammatory, anti-remodeling effects and providing an attractive drug target for the treatment of IPF. This review summarizes knowledge about the association of pulmonary fibrosis with PKE4, as well as emerging preclinical studies and clinical trials regarding PDE4 inhibitors.
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and typical chronic fibrotic lung disease. In recent years, significant progress has been made in the pathophysiology, clinical diagnosis and treatment of IPF. However, to date, there is still no cure for IPF. The second messenger cyclic adenosine monophosphate (cAMP) inhibits fibroblast proliferation or differentiation into myofibroblasts during the development of IPF. Phosphodiesterase 4 (PDE4) is a major camp-degrading enzyme in lung fibroblasts, which is up-regulated during the progression of fibrosis. PDE4 inhibitors have anti-fibrosis effects in vivo and in vitro in IPF models. In addition, PDE4 is widely involved in inflammatory processes, which are also active in the pathogenesis of IPF. Thus, PDE4 inhibition is a potential therapeutic approach for IPF. This article reviews the pathogenesis of IPF and the physiological function of PDE subtype 4 inhibitors in the treatment of IPF.
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology, which is characterized by scarring of lung parenchyma, leading to reduced quality of life and premature death. At present, some studies have confirmed that hypothyroidism (HT) may play a role in the development of fibrosis. Many animal experiments have proved that thyroid hormone (TH) can inhibit pulmonary fibrosis by regulating glucose metabolism, improving mitochondrial function and inhibiting inflammation. This paper summarizes the correlation between TH and IPF, and deeply understands the relationship between TH and IPF, in order to have new treatment strategies for IPF in the future.
ABSTRACT
IPF is a chronic progressive interstitial lung disease of unknown etiology and poor prognosis, and despite receive treatment, most patients consideration are likely to progress or worsen. Integrins are heterodimer cell surface proteins that are promising therapeutic targets for intervention in pulmonary fibrosis. Alphav integrins are central to the development of fibrosis because they activate latent TGF-β, a known pro-fibrosis cytokine. The alphav subunit may form heterodimers with the β1, β3, β5, β6, or β8 subunits, one or more of which are essential for the development of pulmonary fibrosis, but their relative importance is unclear. This review summarizes the knowledge of the association of pulmonary fibrosis with alpha-val-integrins, as well as emerging preclinical studies and clinical trials of alpha-fibrosis inhibitors.
ABSTRACT
【Objective】 To investigate and summarize the clinical and imaging features of a few patients with coronavirus disease 2019 (COVID-19) in Lanzhou City. 【Methods】 We carried out a retrospective analysis of the epidemiological data, laboratory results and clinical imaging features of eight hospitalized patients with confirmed COVID-19 in The First Hospital of Lanzhou University from January 23 to February 23, 2020. 【Results】 The sex ratio (men to women) of the 8 patients was 5∶3 while their age ranged from 24 to 57 years old. The incubation period was 1-10 days. Of the 8 patients, 7(87.5%) had COVID-19 brought in from other places in China and 1(12.5%) was a secondary infection case. The main clinical manifestations included cough in 6 cases (75%), fever in 4 cases (50%), expectoration in 3 cases (37.5%), and fatigue in 2 cases (25%). All the 8 cases indicated abnormal manifestations in blood routine examinations, 4 cases (50%) decreased in WBC, 7 cases (87.5%) decreased in Lym count, 5 cases (62.5%) increased in LDH, 1 case (12.5%) increased in CK, 1 case(12.5%) increased in CK-MB, 4 cases (50%) increased in CRP, 2 cases (25%) increased in PCT, and 1 case (12.5%) increased in D-dimer. Of the 2 patients examined by chest digital radiography (DR), one DR finding was not typical and the other one suggested increased bilateral lung markings. Six patients were examined by HRCT, of whom four (50%) showed multiple ground glass opacities on both lobes and two (25%) showed multiple ground glass opacities only on the right lobe; none of the 6 imaging findings suggested pleural effusion. Six patients were discharged from hospital after being cured and 1 patient still underwent treatment. 【Conclusion】 Most of these 8 patients had COVID-19 imported from outside the city, and the patients were relatively young with few underlying diseases. Their major symptoms were fever, cough, and expectoration. All of them exhibited abnormal findings in blood routine examinations; half of them suggested increased CRP while a few ones showed abnormal CK and Ddimer values. The imaging manifestations of most patients were multiple ground glass opacities near the peripheral pleura.
ABSTRACT
Objective@#To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage.@*Methods@#Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate.@*Results@#32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34- ~ 21.15) mmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31- ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) mmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) mmol/L, respectively.@*Conclusion@#The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.
ABSTRACT
<p><b>BACKGROUND</b>Obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease. Ghrelin and obestatin are two peptides from the same source but have opposite roles. Both of them can affect feeding and regulate vascular tune. The aim of this study was to investigate the relationship between plasma ghrelin, obestatin, the ratio of ghrelin and obestatin (G/O) and sleep parameters and blood pressure circadian rhythms in patients with OSAS.</p><p><b>METHODS</b>This study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS group), 30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30 non-OSAS normal weight adults (control group). Polysomnography (PSG) was performed in the OSAS group and over-weight group. Blood pressure of all subjects was monitored by means of 24-hour ambulatory blood pressure monitoring. The concentration of plasma ghrelin and obestatin was detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Plasma ghrelin levels in the OSAS group and over-weight group were significantly lower than that of the control group (P < 0.05). Plasma obestatin levels were lower in the over-weight group and OSAS group, but there was no significant difference among the three groups. The blood pressure in OSAS patients was higher, and there was a significant difference in all blood pressure parameters compared to the control group, and in the daytime average diastolic blood pressure (DBP), nocturnal average systolic blood pressure (SBP) and DBP, DBP variability values as compared to over-weight subjects. Furthermore, there were significantly more non-dipper patterns of blood pressure (including hypertension and normotension) in the OSAS group than in the other two groups (P < 0.01). Correlation analysis showed that ghrelin levels had a significant correlation with BMI and nocturnal average DBP but not with PSG parameters. In contrast, the G/O ratio had a negative correlation with apnea-hypopnea index (AHI) (P < 0.05), as well as a strong positive correlation with the blood pressure variability values (P < 0.01). In multivariate analyses, AHI (P < 0.05) and G/O (P < 0.05) were independently related to SBP variability changes, while AHI (P < 0.05), G/O (P < 0.01) and BMI (P < 0.05) were independently related to DBP variability changes.</p><p><b>CONCLUSIONS</b>Our data show plasma ghrelin and obestatin levels were related to obesity in OSAS. Sleep apnea in OSAS patients could have led to an imbalance in G/O in the basis of obesity. Moreover, the imbalance may promote nighttime blood pressure elevation and affect blood pressure circadian disorder.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Blood Pressure , Physiology , Circadian Rhythm , Physiology , Enzyme-Linked Immunosorbent Assay , Ghrelin , Blood , Obesity , Blood , Pancreatic Neoplasms , Blood , Prognosis , Repressor Proteins , Metabolism , Sleep Apnea, Obstructive , BloodABSTRACT
Objective To develop a score based on clinical symptoms and signs for evaluating the severity of obstructive sleep apnea syndrome (OSAHS). Methods A total of 158 OSAHS patients were enrolled. Five clinical features,including habitual snore,sleep apnea,daytime sleepiness,obesity and hypertension were used to arrive at a clinical score and its value to evaluate severity of OSAHS was determined. Results The clinical score of the two assessors was (7.94 ± 3.22) and (7.62 ± 3.08) scores respectively and a highly significant positive correlation was obtained (r = 0.97,P= 0.00). The clinical score of mild (43 cases ), moderate(47 cases ) and severe OSAHS ( 68 cases ) was ( 5.53 ± 2.25 ), ( 7.66 ± 2.05 ) and (9.29 ± 2.27) scores respectively,and there was significant difference among three groups (P = 0.00). The general clinical score of the two assessors was (7.78 ± 2.68) scores,the apnea-hypopnea index was 37.15 ±19.53,and there was a significant positive correlation between them (r = 0.70,P= 0.00). By analysis of ROC curves, the cut-off values of clinical score for differentiating moderate-severe OSAHS from mild OSAHS was 7 scores, and the sensitivity, specificity and accuracy was 83.5%, 74.4% and 80.4% respectively. Conclusion Clinical score,with good reliability,validity and high sccuracy,is a simple method to evaluate severity of OSAHS.
ABSTRACT
Objective To evaluate the effect and safety of tiotropium plus sustained-release theophylline in treating stable moderate chronic obstructive pulmonary diseases (COPD) . Methods A randomized clinical trail was conducted in 80 patients with stable moderate COPD, who were admitted to our hospital from March 2008 to December 2009. All patients were divided into two groups randomly and accepted tiotropium (groupⅠ ,n =40) or tiotropium plus sustained-release theophylline (group Ⅱ ,n =40) treatment for 12 weeks. Results Seventy patients completed the study,in which 36 cases had tiotropium alone and 34 cases had combination therapy. At the end of treatment, no statistically significant difference was found between the two groups in the comparisons of FEV1, FEV1%, FVC, FEV1/FVC, activity score and impacts score of the St George's Respiratory Questionnaire (SGRQ) (Ps > 0. 05). While the symptoms score (53.08 ± 12.25 vs.59.39±9.74,t=2.39,P 0. 05). Conclusion Compared with the single application of tiotropium, tiotropium plus sustained-release theophylline therapy can alleviate symptoms and improve life quality in patients with stable moderate COPD,without significantly increasing adverse reactions.
ABSTRACT
Objective To study the changes of serum high-sensitivity C-reactive protein (ha-CRP) and depression in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS),and investigate the relationship between them.Methods Thirty healthy volunteers (control group) and 54 OSAHS patients (OSAHS group) were recruited for the study.The level of serum hs-CRP was determined by scatter rate nephelometry,and the state of depression was assessed by self-rating depression scale (SDS).Results The level of serum hs-CRP and SDS score were higher in OSAHS group than those in control group [(48.8 ± 12.7) scores vs.(36.3 ± 6.3) scores,(3.3 ±0.7) mg/L vs.(1.4 ± 0.4) mg/L](P＜0.01).SDS score and the level of serum hs-CRPwere positively correlated to apnea-hypopnea index(AHI) (r = 0.636,0.628 ;P<0.01) and negatively related to the MSaO2 (r =-0.509,-0.614;P <0.01) and LSaO2 (r =-0.607,-0.512;P <0.01).The level of serum hs-CRP was positive correlation to SDS score (r = 0.536,P<0.01).SDS score was related to the AHI,the level of serum hs-CRP and LSaO2 in multiple linear regression(F= 33.31,P = 0.002).Conclusion Depression is correlated to AHI and the level of serum hs-CRP in patients with OSAHS.
ABSTRACT
Objective To study the polysomnography(PSG) indexes which can reflex the severity of anoxia in obstructive sleep apnea-hypopnea syndrome(OSAHS) more comprehensively. Methods Sixtythree OSAHS patients' PSG indexes, including the apnea-hypopnea index (AHI), apnea time/total sleeping time (AM), hypoventilation time/total sleeping time (HM), mean oxygen saturation (MSaO2),the lowest oxygen saturation (LSaO2) and the longest apnea time (LAT) were analyzed retrospectively. Results In patients with OSAHS,the AHI was positively correlated with AM, HM and LAT(P ＜ 0.01 or ＜ 0.05 ), and was negatively correlated with MSaO2 and LSaO2(P ＜ 0.01 ). The AHI had linear regression relationship with AM,HM and LSaO2 (F =202.264,P ＜0.01). Conclusions Among the PSG indexes,AM is intimately associated with AHI. Therefore,compared with LSaO2,AM and HM can reflex the severity of anoxia in patients with OSAHS more accurately.
ABSTRACT
Objective To investigate the role of RhoA/Rho associated kinase-2 (RhoA/ROCK-2) in the development of pulmonary hypertension (PH) in patients with obstructive sleep apnea-hypopnea syndrome (OS-AHS). Methods Thirty patients diagnosed as OSAHS by polysomnograshy(PSG) test in our sleep laberatoty were recruited as the observation group, and fifteen healthy subjects matched in gender, age and body mass index (BMI) were recruited as the controls. Pulmonary arterial pressure was measured by echocardiography. Serum RhoA/ROCK-2 levels were measured. Results The level of PAP was (47.30±12.85)mm Hg in OSAHA patients complicated with PH, (22.31±3.07)mm Hg in OSAHA patients without PH, which were significantly higher than that in the controls (19.47±1.92) mm Hg (W=175.50, P < 0.05). The serum RhoA and ROCK-2 in OSAHA patients with-out PH (10.43±3.10 and 22.31±16.10 μ/L, respectively) were significantly higher those in the controls (2.94±1.20)μg/L and (6.04±0.28)μg/L, respectively) (W=120.00, W= 121.00, respectively, P<0.05), whereas significantly lower than that in OSAHA patients complicated with PH(14.85±8.49)μg/L, (36.81±12.69) μg/L, respectively) (H =29.172, H =30.242, respectively, P <0.05). There was a positive correlation between PAP and AHI in patients with OSAHS, whether complicated with PH or not(r_s=0.793, r_s=0.887,P <0.05), and there was a negative correlation between PAP and LSaO2 in patients with OSAHS (r_s=-0. 562,r_s = -0.751, P <0.05). There were positive correlations between the level of RboA/ROCK-2 and PAP in patients with OSAHS(r_s = 0.793,r_s = 0.887,P < 0.05). Finally, there was a positive correlation between the level of RhoA and ROCK-2 in patients with OSAHS (r_s = 1.000,r_s = 1.000,P < 0.05). Conclusions OSAHS is an inde-pendent risk factor for pulmonary hypertension. The levels of serum RhoA/ROCK-2 in OSAHS patients with PH were increased in the development of the disease. It may play an important role in the process of pulmonary hyper-tension in patients with OSAHS.
ABSTRACT
Objective To study the effect of inducible nitric oxide synthase(iNOS)on the occurrence of ischemic cerebral stroke in passive smoking female.Methods 100 passive smoking female patients with ischemic cerebral stroke(passive smoking group) according to the passive smoking index were divided into sub-groups index 900;25 cases in each group.The level of serum iNOS and the situation of carotid atherosclerosis were detected.The resules were compared with healthy female who without smoking and passive smoking(normal control group).Results Compared with the normal control group,the levels of serum iNOS,the intimal media thickness(IMT)s of carotid artery and the positive rates of carotid atherosclerosis plaque in each passive smoking index sub-group were significantly increased(all P