Open Access

Inflammatory cytokines tumor necrosis factor‑α, interleukin‑8 and sleep monitoring in patients with obstructive sleep apnea syndrome

  • Authors:
    • Hao Ming
    • Aimin Tian
    • Bing Liu
    • Yuqiang Hu
    • Chen Liu
    • Renjie Chen
    • Liangjun Cheng
  • View Affiliations

  • Published online on: December 18, 2018     https://doi.org/10.3892/etm.2018.7110
  • Pages: 1766-1770
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The present study investigated the changes of tumor necrosis factor‑α (TNF‑α), interleukin‑8 (IL‑8) and sleep ability in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 684 patients who were admitted to Xuzhou Central Hospital between June 2012 and June 2016 were enrolled to serve as the experimental group and 192 healthy subjects were selected as the control group. Polysomnography was performed on both groups, and serum TNF‑α and IL‑8 levels were measured by ELISA. Pearson's correlation analysis was used to analyze correlations between factors. Compared with control group, the levels of TNF‑α and IL‑8, the morning systolic and diastolic pressure in OSAHS group were significantly higher (P<0.01). Furthermore, the mean oxygen saturation (MSaO2) and lowest oxygen saturation (LSaO2) of the OSAHS group were significantly lower compared with those in control group (P<0.01). Results also indicated that TNF‑α was positively correlated with apnea‑hypopnea index (AHI), morning systolic and diastolic pressure (r=0.621, 0.464, 0.539; P<0.05), and negatively correlated with MSaO2 and LSaO2 (r=‑0.526, ‑0.466; P<0.05). Notably, IL‑8 was positively correlated with AHI, morning systolic and diastolic pressure (r=0.337, 0.413 and 0.629; P<0.05), and negatively correlated with MSaO2 and LSaO2 (r=‑0.329 and ‑0.417; P<0.05). Therefore, it was concluded that TNF‑α and IL‑8 may be involved in the occurrence and development of OSAHS, are closely related to OSAHS and may be important risk factors for cardiovascular disease in patients with OSAHS. The present findings suggest that TNF‑α and IL‑8 can be used to assess the degree of OSAHS.

Introduction

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a potentially lethal respiratory sleep disorder that, in recent years, has attracted increasing attention. It mainly affects middle-aged obese men, and the main pathogenesis is the collapse of the upper airway during sleep. Symptoms of OSAHS such as snoring, daytime drowsiness and nocturia can be easily ignored by patients. The recurrence of the disease can cause coronary heart disease and cerebrovascular disease, and sudden deaths can even occur at night (1,2). It has been reported that OSAHS affects ~5% of male adults worldwide (3), and its incidence is still increasing. OSAHS is related to a variety of inflammatory factors. In OSAHS patients, the levels of proinflammatory cytokines are increased, and the level of anti-inflammatory factors are decreased, eventually causing endothelial dysfunction (4). Interleukin-8 (IL-8) is a multifunctional chemokine that causes neutrophils to leave the bloodstream and travel to lesions. IL-8 is significantly increased in patients with respiratory diseases such as pulmonary fibrosis, respiratory distress syndrome, bronchitis and bronchiectasis (5). Tumor necrosis factor-α (TNF-α), as a relatively common cytokine, is mainly secreted by adipocytes and mononuclear-macrophage system. TNF-α regulates the immune system, induces inflammation, and participates in the regulation of fat metabolism. TNF-α in the blood of OSAHS patients is usually increased compared with healthy subjects (6). IL-8 and TNF-α levels are increased in inflammatory response of various diseases, but their involvement in OSAHS has not been well studied. In this study, we investigated the changes of TNF-α, IL-8 and sleep ability in patients with OSAHS to investigate their correlations with OSAHS.

Patients and methods

Research subjects

A total of 684 OSAHS patients admitted to Xuzhou Central Hospital from June 2012 to June 2016 were enrolled in this study. Among them, 446 were males and 238 were females, with an average age of 51.34±5.16 years (experimental group). A total of 192 healthy subjects were selected at the same period to serve as control group. Control group included 128 males and 64 females, with an average age of 52.18±4.51 years (control group). The two groups had no significant difference in terms of sex, age, or other general data, but had significant difference in the Pittsburgh sleep quality index (P<0.001) (Table I). Inclusion criteria: >48 years old and body mass index (BMI) ranging from 24.1 to 30.5 kg/m2. All patients with OSAHS met the diagnostic criteria of OSAHS diagnosis guideline set by the Respiratory Disease Branch of Chinese Medical Association. Exclusion criteria: patients with incomplete data or patients that could not cope with clinical diagnosis; patients with a history of cancer, nervous system diseases, other respiratory diseases, coronary heart disease, renal dysfunction, and other inflammatory diseases that could affect the experiment. The study was approved by the Ethics Committee of Xuzhou Central Hospital (Xuzhou, China), and all the subjects or their relatives signed an informed consent.

Table I.

Clinical data of 876 subjects [n (%)].

Table I.

Clinical data of 876 subjects [n (%)].

Basic informationExperimental group (n=684)Control group (n=192)χ2P-value
Sex 0.1420.732
  Male446 (65.20)128 (66.67)
  Female238 (34.80)64 (33.33)
Age (years) 0.0280.928
  ≥50491 (71.78)139 (72.40)
  <50193 (28.22)53 (27.60)
Ethnicity 0.4710.452
  Han653 (95.47)181 (94.27)
  Other31 (4.53)11 (5.73)
Marital status 0.9170.640
  Married639 (93.42)181 (94.27)
  Divorced41 (5.99)9 (4.69)
  Unmarried4 (0.58)2 (1.04)
Major changes in recent living habits 2.0470.171
  Yes13 (1.90)7 (3.65)
  No671 (98.10)185 (96.35)
Lifestyle and habits 0.2360.672
  Closed247 (36.11)73 (38.02)
  Open437 (63.89)119 (61.98)
Pittsburgh sleep quality index 36.612<0.001
  ≤7237 (34.65)113 (58.85)
  ≥8447 (65.35)79 (41.15)
BMI (kg/m2) 1.9790.165
  ≥27367 (53.65)92 (47.92)
  <27317 (46.35)100 (52.08)
Diabetes 2.4130.131
  Yes59 (8.63)10 (5.21)
  No625 (91.37)182 (94.79)
Metabolic syndrome 1.6990.276
  Yes18 (2.63)2 (1.04)
  No666 (97.37)190 (98.96)

[i] BMI, body mass index.

Experimental reagents and equipment

TNF-α was detected using human TNF-α high sensitivity ELISA kit [Thermo Fisher (Shanghai) Co., Ltd., Shanghai, China]; IL-8 assay was performed using human IL-8 enzyme immunoassay kit [Thermo Fisher (Shanghai) Co., Ltd.]; immunoassay analyzer was UniCel DxI 800 automated chemiluminescence immunoassay analyzer [Beckman Coulter (Shanghai) Co., Ltd., Shanghai, China], and sleep monitoring was performed by using Alice LE multi-channel sleep monitor (Beijing Weikang Medical Devices, Beijing, China).

Experimental method

All subjects underwent polysomnography. Fasting venous blood (5 ml) was drawn from the subjects after the second morning of monitoring. Serum TNF-α and IL-8 levels were measured by ELISA. All specimens were frozen and stored at −20°C.

Polysomnography

Patients were not allowed to take sedative drugs or food and drinks that could stimulate the nervous system 24 h prior to polysomnography detection. Sleep monitoring was performed in the hospital for >7 h using polysomnography. Index data were recorded after manual check at the end of monitoring. Indexes included early morning diastolic and systolic blood pressure, mean oxygen saturation (MSaO2), lowest oxygen saturation (LSaO2), and apnea-hypopnea index (AHI).

TNF-α and IL-8 detection methods

According to the manufacturer's instructions of ELISA kit, the reagent was removed from the refrigerator and placed at room temperature for 20 min before use, and the concentrated wash liquid was diluted with distilled water to a ratio of 1:20. Blank wells were set, and specimens or different concentrations of standard solution (100 µl/well) were added into the corresponding well. The wells were sealed with plastic sheet and incubated at 37°C constant temperature for 90 min. Washing was performed every 25 sec for 4 times. After that, biotin mouse anti-human TNF-α and IL-8 monoclonal antibody (1:600; cat. nos. AHC3419 and M802B; Thermo Fisher Scientific, Inc., Waltham, MA, USA) was added into each well (100 µl/well), except the blank wells. After incubation at 37°C for 60 min, the plate was washed 4 times. Chromogenic reagent was added into each well (100 µl/well), followed by incubation at 37°C for 20 min in the dark. Finally, stop solution was added into each well (100 µl/well), and OD450 value was measured within 5 min. TNF-α and IL-8 content in serum was calculated according to the standard curve. The minimum detectable dose of human TNF-α level was 4 pg/ml, and intra- and inter-plate coefficient of variation was <10%. The minimum detectable dose of human IL-8 was 3.9 pg/ml, and intra- and inter-plate coefficient of variation was <10%.

Statistical analysis

SPSS 18.0 (Tianjin Soft Network Technology Co., Ltd., Tianjin, China) software was used for all analyses. Enumeration data were expressed as n (%), and were compared by ×2 test. Measurement data were expressed as (mean ± SD) and were compared by t-test. Correlation analysis was performed using Pearson's correlation coefficient analysis. P<0.05 was considered to indicate a statistically significant difference.

Results

Comparison of serum levels of TNF-α and IL-8 between two groups

Levels of TNF-α and IL-8 in the experimental group were 31.2±5.3 and 34.6±7.1 pg/ml, respectively, while those in the control group were 12.1±1.1 and 19.4±8.5 pg/ml, respectively (Table II). The levels of TNF-α and IL-8 in the experimental group were significantly higher than those in the control group (P<0.05).

Table II.

Comparison of TNF-α and IL-8 levels between two groups (mean ± SD).

Table II.

Comparison of TNF-α and IL-8 levels between two groups (mean ± SD).

IndexExperimental group (pg/ml)Control group (pg/ml)tP-value
TNF-α31.2±5.312.1±1.149.620<0.001
IL-834.6±7.119.4±8.525.050<0.001

[i] TNF-α, tumor necrosis factor-α; IL-8, interleukin-8.

Polysomnography results

Morning systolic blood pressure in experimental group was 139±9 mmHg, and in control group 119±8 mmHg. Morning systolic blood pressure in experimental group was significantly higher than that in control group (P<0.001). Morning diastolic blood pressure in experimental group was 88±7 mmHg, and in control group 75±6 mmHg. Morning diastolic blood pressure in experimental group was significantly higher than that in control group (P<0.001). MSaO2 was 73.19±7.65% in experimental group and 97.01±2.16% in control group. MSaO2 in experimental group was significantly lower than that in control group (P<0.001). LSaO2 was 50.87±9.24% in experimental group, and 84.71±3.84% in control group. LSaO2 was significantly lower in experimental group than in control group (P<0.001). AHI in experimental group was 31.15±9.12/h, and in control group 4.34±2.01/h. AHI in experimental group was significantly higher than that in control group (P<0.001) (Table III).

Table III.

Comparison of polysomnography results between two groups.

Table III.

Comparison of polysomnography results between two groups.

IndexExperimental group (n=684)Control group (n=192)tP-value
Morning systolic blood pressure (mmHg)139±9119±827.860<0.001
Morning diastolic blood pressure (mmHg)88±775±623.430<0.001
MSaO2 (%)73.19±7.6597.01±2.1642.650<0.001
LSaO2 (%)50.87±9.2484.71±3.8449.540<0.001
AHI (times/h)31.15±9.124.34±2.0140.440<0.001

[i] MSaO2, mean oxygen saturation; LSaO2, lowest oxygen saturation; AHI, apnea-hypopnea index.

Correlation analysis of ELISA and polysomnography monitoring results

Serum levels of TNF-α were positively correlated with AHI, morning systolic and diastolic pressure (r=0.621, 0.464 and 0.539, P<0.05), but negatively correlated with MSaO2 and LSaO2 (r=−0.526 and −0.466, P<0.05). There was a positive correlation of IL-8 with AHI, morning systolic and diastolic pressure (r=0.337, 0.413 and 0.629, P<0.05), but negative correlation with MSaO2 and LSaO2 (r=−0.329 and −0.417, P<0.05) (Table IV).

Table IV.

ELISA and polysomnography monitoring correlation analysis.

Table IV.

ELISA and polysomnography monitoring correlation analysis.

IndexTNF-αIL-8
AHI
  r0.6210.337
  P-value<0.05<0.05
Morning systolic blood pressure
  r0.4640.413
  P-value<0.05<0.05
Morning diastolic blood pressure
  r0.5390.629
  P-value<0.05<0.05
MSaO2
  r−0.526−0.329
  P-value<0.05<0.05
LSaO2
  r−0.466−0.417
  P-value<0.05<0.05

[i] TNF-α, tumor necrosis factor-α; IL-8, interleukin-8; AHI, apnea-hypopnea index; MSaO2, mean oxygen saturation; LSaO2, lowest oxygen saturation.

Discussion

Diagnosis of OSAHS is mainly based on the comprehensive evaluation of the patient's symptoms and the results of polysomnography (7,8), which may cause diagnostic errors. OSAHS symptoms of snoring and nocturia can be easily misdiagnosed as asthma, pharyngitis and other diseases (911), leading to delayed treatment and occurrence of cardiovascular disease, seriously affecting the quality of life of patients. Therefore, the development of more sensitive diagnostic markers for OSAHS is urgently needed.

Our results showed that the expression levels of TNF-α and IL-8 in experimental group were significantly higher than those in the control group, suggesting that TNF-α and IL-8 may be involved in the occurrence and development of OSAHS. TNF-α is a small molecule protein secreted by macrophages. TNF-α has a variety of inflammatory biological functions (12), and most of OSAHS patients are affected by throat inflammation, which can cause changes in the levels of a series of inflammatory mediators, including the increased TNF-α release (13). Increased release of TNF-α may result in delipidation of cells, leading to procoagulant activity and the deposition of fibrin, which in turn increases the production of peroxide and damages the cardiovascular system (14). TNF-α may also promote neovascularization and formation of atherosclerosis (15), leading to the occurrence of cardiovascular complications and heart failure in OSAHS patients. Furthermore, TNF-α causes increased expression of adhesion molecules on the vascular endothelial cells and leukocytes, leading to accelerated activation of lymphocytes, causing severe inflammatory reactions in lesion area (16). Strengthened adhesion of endothelial cells and other cells may cause the formation of microcirculation channel blockage to affect blood supply to tissues, resulting in severe hypoxia in OSAHS (17). IL-8 has a strong influence on the activation, regulation and chemotactic effect of neutrophils,. Akyol et al (18) have reported that IL-8 binds to surface-specific receptor of neutrophils, which will lead to cell deformation, degranulation and the increased generation of reactive oxygen species. This process may induce the production of lysosomes to activate arachidonic acid, leading to increased vascular permeability, plasma protein exudation, resulting in tissue damage, atherosclerosis and other diseases (19). Changes in the levels of TNF-α and IL-8 in patients with OSAHS are related to the activation of inflammatory reaction and abnormal production, and accumulation of these two factors may induce chemotactic infiltration of inflammatory cells and endothelial cell injury, which is an important risk factor for atherosclerosis.

Results of polysomnography showed that morning diastolic and systolic pressure were higher in experimental group than those in control group. These two indicators in the experimental group almost reached the critical point of international standard of hypertensive, indicating that patients in the experimental group had developed or tended to have symptoms of hypertension. MSaO2 and LSaO2 of the control group were higher than those in the experimental group. AHI of the control group was lower than that of the experimental group. Due to abnormal expression of TNF-α in patients with OSAHS, the microcirculation channel is blocked (20) and the upper airway collapses, resulting in increased frequency of low ventilation. Increased hypoventilation can also cause decreased MSaO2 and LSaO2, and decreased blood oxygen concentration, which in turn lead to the dormancy of functional cells (21). Correlation analysis showed that TNF-α and IL-8 were positively correlated with AHI, morning systolic and diastolic blood pressure, but were negatively correlated with MSaO2 and LSaO2. Elevated levels of TNF-α and IL-8 may cause cell deformation, increased adhesion of endothelial cells, which may lead to blockage of blood vessel wall and airway. Blocked blood vessel wall and airway aggregates hypoventilation, abnormal blood pressure and reduced blood oxygen levels, causing increased severity of the disease (22).

In summary, TNF-α and IL-8 may participate in the development of OSAHS. TNF-α and IL-8 may serve as important markers for the diagnosis of OSAHS and the prediction of the severity of disease, and serve as an important basis for assessing the degree of disease in patients with OSAHS. A treatment focusing on these two factors can effectively prevent the occurrence of cardiovascular disease and improve the patients' quality of life.

Acknowledgements

Not applicable.

Funding

No funding was received.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors' contributions

HM wrote the manuscript. HM and AT recorded and analyzed the polysomnography data. HM, BL and YH treated the patients. CL and LC were responsible for ELISA. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of Xuzhou Central Hospital (Xuzhou, China) and informed consents were signed by the patients or the guardians.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

Gaines J, Kong L, Li M, Fernandez-Mendoza J, Bixler EO, Basta M and Vgontzas AN: C-reactive protein improves the ability to detect cardiometabolic risk in mild-to-moderate obstructive sleep apnea. Physiol Rep. 5(pii): e134542017. View Article : Google Scholar : PubMed/NCBI

2 

Oikonomakis K, Petrelli M, Andreanos K, Mouchtouris A, Petrou P, Georgalas I, Papaconstantinou D and Kymionis G: Corneal neovascularization with associated lipid keratopathy in a patient with obstructive sleep apnea-hypopnea syndrome using a continuous positive airway pressure machine. Case Rep Ophthalmol. 8:416–420. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Nadeem R, Singh M, Nida M, Kwon S, Sajid H, Witkowski J, Pahomov E, Shah K, Park W and Champeau D: Effect of CPAP treatment for obstructive sleep apnea hypopnea syndrome on lipid profile: A meta-regression analysis. J Clin Sleep Med. 10:1295–1302. 2014.PubMed/NCBI

4 

Kleisiaris CF, Kritsotakis EI, Daniil Z, Tzanakis N, Papaioannou A and Gourgoulianis KI: The prevalence of obstructive sleep apnea-hypopnea syndrome-related symptoms and their relation to airflow limitation in an elderly population receiving home care. Int J Chron Obstruct Pulmon Dis. 9:1111–1117. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Adedayo AM, Olafiranye O, Smith D, Hill A, Zizi F, Brown C and Jean-Louis G: Obstructive sleep apnea and dyslipidemia: evidence and underlying mechanism. Sleep Breath. 18:13–18. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Rodriguez-Roisin R, Anzueto A, Bourbeau J, DeGuia T, Hui D and Jenkins C: From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014. simplehttps://goldcopd.org/

7 

Tang SX, Qing J, Wang YW, Chai L, Zhang WM, Ye XW, Zhang J, Huang YQ and Cheng P: Clinical analysis of pharyngeal musculature and genioglossus exercising to treat obstructive sleep apnea and hypopnea syndrome. J Zhejiang Univ Sci B. 16:931–939. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Quinnell TG, Bennett M, Jordan J, Clutterbuck-James AL, Davies MG, Smith IE, Oscroft N, Pittman MA, Cameron M and Chadwick R: A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO). Thorax. 69:938–945. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Wang Q, Zhang C, Jia P, Zhang J, Feng L, Wei S, Luo Y, Su L, Zhao C, Dong H, et al: The association between the phenotype of excessive daytime sleepiness and blood pressure in patients with obstructive sleep apnea-hypopnea syndrome. Int J Med Sci. 11:713–720. 2014. View Article : Google Scholar : PubMed/NCBI

10 

White DP: New therapies for obstructive sleep apnea. Semin Respir Crit Care Med. 35:621–628. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Zhang Q, Zhang X, Zhao M, Huang H, Ding N, Zhang X and Wang H: Correlation of obstructive sleep apnea hypopnea syndrome with metabolic syndrome in snorers. J Biomed Res. 28:222–227. 2014.PubMed/NCBI

12 

Young LR, Taxin ZH, Norman RG, Walsleben JA, Rapoport DM and Ayappa I: Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. Sleep. 36:405–412. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Camacho M, Certal V, Abdullatif J, Zaghi S, Ruoff CM, Capasso R and Kushida CA: Myofunctional therapy to treat obstructive sleep apnea: A systematic review and meta-analysis. Sleep. 38:6692015. View Article : Google Scholar : PubMed/NCBI

14 

Camacho M, Certal V and Capasso R: Comprehensive review of surgeries for obstructive sleep apnea syndrome. Braz J Otorhinolaryngol. 79:780–788. 2013.(In Portuguese). View Article : Google Scholar : PubMed/NCBI

15 

Eckert DJ, White DP, Jordan AS, Malhotra A and Wellman A: Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Crit Care Med. 188:996–1004. 2013. View Article : Google Scholar

16 

Xiao SC, He BT, Steier J, Moxham J, Polkey MI and Luo YM: Neural respiratory drive and arousal in patients with obstructive sleep apnea hypopnea. Sleep. 38:941–949. 2015.PubMed/NCBI

17 

Eckert DJ and Younes MK: Arousal from sleep: Implications for obstructive sleep apnea pathogenesis and treatment. J Appl Physiol. 116:302–313. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Akyol S, Çörtük M, Baykan AO, Kiraz K, Börekçi A, Şeker T, Gür M and Çayli M: Mean platelet volume is associated with disease severity in patients with obstructive sleep apnea syndrome. Clinics (Sao Paulo). 70:481–485. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Azagra-Calero E, Espinar-Escalona E, Barrera-Mora JM, Llamas-Carreras JM and Solano-Reina E: Obstructive sleep apnea syndrome (OSAS). Review of the literature. Med Oral Patol Oral Cir Bucal. 17:e925–e929. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Weinstock TG, Rosen CL, Marcus CL, Garetz S, Mitchell RB, Amin R, Paruthi S, Katz E, Arens R and Weng J: Predictors of obstructive sleep apnea severity in adenotonsillectomy candidates. Sleep. 37:261–269. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Enderling H: Cancer stem cells and tumor dormancy. Adv Exp Med Biol. 734:55–71. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Pandey S, Misra SK and Sharma N: Ethosomes - a novelize vesicular drug delivery system. Res J Pharm Technol. 10:3223–3232. 2017. View Article : Google Scholar

Related Articles

Journal Cover

March-2019
Volume 17 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ming H, Tian A, Liu B, Hu Y, Liu C, Chen R and Cheng L: Inflammatory cytokines tumor necrosis factor‑α, interleukin‑8 and sleep monitoring in patients with obstructive sleep apnea syndrome. Exp Ther Med 17: 1766-1770, 2019
APA
Ming, H., Tian, A., Liu, B., Hu, Y., Liu, C., Chen, R., & Cheng, L. (2019). Inflammatory cytokines tumor necrosis factor‑α, interleukin‑8 and sleep monitoring in patients with obstructive sleep apnea syndrome. Experimental and Therapeutic Medicine, 17, 1766-1770. https://doi.org/10.3892/etm.2018.7110
MLA
Ming, H., Tian, A., Liu, B., Hu, Y., Liu, C., Chen, R., Cheng, L."Inflammatory cytokines tumor necrosis factor‑α, interleukin‑8 and sleep monitoring in patients with obstructive sleep apnea syndrome". Experimental and Therapeutic Medicine 17.3 (2019): 1766-1770.
Chicago
Ming, H., Tian, A., Liu, B., Hu, Y., Liu, C., Chen, R., Cheng, L."Inflammatory cytokines tumor necrosis factor‑α, interleukin‑8 and sleep monitoring in patients with obstructive sleep apnea syndrome". Experimental and Therapeutic Medicine 17, no. 3 (2019): 1766-1770. https://doi.org/10.3892/etm.2018.7110