| Background:Sleep is an essential activity of human life.Good sleep is of great significance to our health.However,with the development of modern society,the average sleep duration is shortened and sleep deprivation becomes more and more prevalent due to the use of electronic media and the advancing pressure from occupational demands.Sleep deprivation includes lack of quality or quantity of sleep.Acute sleep deprivation is defined as the elimination of sleep for at least 16-18 hours.Chronic sleep deprivation occurs when multiple nights get too little sleep or poor sleep quality,such as sleep disorders and shift work.It is reported that sleep deprivation affects the secretion of hormones,leading to endocrine and metabolic disorders,and increasing the risks of diabetes and thyroid diseases.Transcriptome is a discipline used to study the structure and function of genes on a holistic level,and it can quickly and completely obtain all transcripts in tissues or cells at a certain time.Transcriptionomic analysis is sensitive and fast,and has been gradually applied to the field of human sleep research.As a fluid matrix,blood connects the entire biological system at the physiological level.It was found that changes in blood transcriptome not only reflect changes in leukocytes of the immune system,but also indicate differences in gene expression throughout the whole organism.The blood transcriptome analysis is a very suitable research method of this subject.Studies have shown that sex differences influence the response to sleep loss as well as the risk for sleep related disorders.However,female was less concerned in published transcriptome studies on sleep deprivation.In addition,it is not clear whether people experiencing chronic sleep deprivation respond differently to acute sleep deprivation when compared with normal control.Objective:The purpose of this study was to study the effects of chronic and acute sleep deprivation on thyroid function in female through whole blood transcriptome analysis,and thus to provide new ideas to explore sleep loss associated health problems.Methods:In this study,we enrolled 11 females,including 6 in chronic sleep deprivation(CSD)group and 5 in normal control(NC)group.Participants of CSD group were nurses from Shandong Provincial Hospital,with a recent consecutive shift work experience of more than 3 months.NC group was control group in which participants slept well and had no sleep deprivation experience in recent 3 months.Blood samples were taken at 8:00am following baseline sleep,acute sleep deprivation(24 hours without sleep)and recovery sleep.The serum adrenocorticotropic hormone(ACTH),cortisol(COR),free triiodothyronine(FT3),free thyroxine(FT4),triiodothyronine(T3),thyroxine(T4),thyroid-stimulating hormone(TSH),insulin(INS),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and lipoprotein(a)(Lpa)were assayed and whole blood transcriptome was analyzed.The comparison of baseline level between CSD and NC was considered as the effect of chronic sleep deprivation,while the comparison of 24 hours prolonged wakefulness with baseline level as the effect of acute sleep deprivation.Results:1.Chronic sleep deprivation affects thyroid functionSerum hormones and biochemical parameters showed that no significant differences existed concerning the levels of serum ACTH,COR,INS and lipids between CSD and NC groups.The basal levels of FT3(5.25±0.38 vs.4.32±0.53,P=0.008)?T3(2.02± 0.21 vs.1.73 ± 0.20,P=0.043)?FT3/FT4(0.32 ± 0,06 vs.0.23± 0.03,P=0.011)and T3/T4(0.019±0.003 vs.0.015±0.001,P=0.020)in CSD were significantly higher,FT4(16.66 ± 1.85 vs.18.85±1.01,P=0.043)was lower in CSD than NC.In addition,TSH level was slightly increased whereas T4 was decreased in CSD group,although with no statistical significances.2.Chronic sleep deprivation affects genes mainly involved with the immune functionIn order to explore the effect of sleep deprivation on thyroid function,in molecular level,whole blood transcriptome analysis was performed by using high-throughput sequencing.In all,1,032 genes showed variations in transcription level due to chronic sleep deprivation,with 578 differentially expressed genes(DEGs)increased and 454 DEGs decreased.The Gene Ontology(GO)enrichment analyses of these genes were primarily associated with neutrophil activation and neutrophil mediated immunity.3.The effect of acute sleep deprivation on thyroid functionThere were significant effects of day on FT3(F2,10=23.84,P<0.001),FT4(F2,10=7.43,P=0.011),T3(F2,10=9.90,P=0.004)and T4(F2,10=6.34,P=0.015)concentrations in CSD group,with significantly higher levels of FT3(6.02±0.33 nmol/L vs.5.25±0.38 nmol/L,P=0.001),FT4(18.55 ± 2.71 vs.16.66±1.85,P=0.042)and T3(2.40±0.34 vs.2.02 ± 0.21,P=0.040)after acute sleep deprivation than baseline.In NC group,there was similar significant effect of day on TSH(F2,8=12.07,P=0.004)with slightly higher levels after acute sleep deprivation than baseline sleep,although post hoc analysis with no significance.4.The effect of acute sleep deprivation on immune functionIn CSD group,acute sleep deprivation resulted in 672 DEGs,among which 525 DEGs were up-regulated and 147 were down-regulated.In NC group,a total of 227 DEGs were found with 158 up-regulated and 69 down-regulated.In CSD group,up-regulated DEGs enriched in biological process(BP)were mostly involved in interleukin-6(IL-6)production,IL-8 production,and neutrophil activation.In NC group,the significant BP terms enriched based on up-regulated DEGs were mainly related to the oxygen transport,response to oxidative stress and regulation of hemopoiesis.Enrichment analysis of down-regulated DEGs in CSD and NC groups did not show any statistical variation.Summary and conclusions:1.Chronic sleep deprivation affects thyroid function in female.2.Whole blood transcriptome analysis showed that chronic sleep deprivation mainly impacted biological processes related to immune function in female.3.Acute sleep deprivation affects thyroid and immune function in female.The thyroid and immune function of female experiencing chronic sleep deprivation were relatively more sensitive to acute sleep deprivation than those with normal sleep.4.The consistency of changes between thyroid and immune function when female exposed to sleep deprivation suggest that the effect of sleep deprivation on thyroid function may be associated with activated immune system.Background:Hypokalemia is the most common electrolyte disorder with serum potassium concentrations<3.5mmol/L.Endocrine and metabolic diseases,gastrointestinal diseases,kidney diseases,drugs using and other diseases may reduce serum potassium concentrations by decreasing potassium intake,increasing intracellular potassium transport and abnormal potassium loss.Hypokalemia can be further divided into mild hypokalemia(K+3.0-3.5mmol/L),moderate hypokalemia(K+2.5-3.Ommol/L)and severe hypokalemia(K+<2.5mmol/L)according to the serum potassium levels.Mild hypokalemia is generally asymptomatic,while severe hypokalemia is associated with life-threatening complications such as arrhythmia and respiratory paralysis.And it is difficult to diagnose and treat hypokalemia due to its complicated etiology,various clinical manifestation,and high recurrence rate.In total,it is necessary to raise our awareness and attention to hypokalemia.Objective:This study aims to explore the causes,clinical features of hypokalemia and related influencing factors of moderate to severe hypokalemia,and thus to provide evidence for the prevention and diagnosis of hypokalemia.Methods:1.Study participantsThe clinical data of 554 hospitalized patients with hypokalemia in the endocrinology department of Shandong provincial hospital during January 2006 and December 2018 were retrospectively analyzed.2.Data collectionThe clinical data of each patient were collected,including age,gender,height,weight,blood pressure,the causes of hypokalemia,and serum potassium,free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),triglycerides(TG),total cholesterol(TC),low-density lipoprotein-cholesterol(LDL-C),high-density lipoprotein-cholesterol(HDL-C),fasting plasma glucose(FPG),carbon dioxide combining power(CO2CP)and creatinine(Crea)levels.3.Statistical analysesAll statistical analyses were performed using SPSS version 22.0 for Windows.Quantitative data were expressed as mean ± standard deviation or median(interquartile range),and comparisons of variance among groups were performed using one-way ANOVA and Kruskal-Wallis test for normally distributed variables and non-normally distributed variables,respectively.Values for categorical variables were presented as number(percentage),and differences among groups were analyzed using chi-squared test.Risk factors of moderate to severe hypokalemia were performed by logistic regression analysis.Differences were considered significant at P<0.05.Results:1.Diabetes,hyperthyroidism and primary aldosteronism are common causes of hypokalemiaDiabetes topped the list involving 109 cases(19.68%)of the entire hypokalemia while hyperthyroidism and primary aldosteronism were diagnosed in 95 cases(17.15%)and 64 cases(11.55%),respectively.2.There are significant differences in gender,age,TC,LDL-C,FT3,FT4 and CO2CP levels among different degrees of hypokalemiaThere were 554 cases of hypokalemia in our study,among whom 227(40.97%)cases were mild hypokalemia,173(31.23%)cases were moderate hypokalemia,and 154 cases(27.80%)were severe hypokalemia.There were significant differences in gender,age,TC,LDL-C,FT3,FT4 and CO2CP levels among different degrees of hypokalemia.Compared to patients with mild hypokalemia,patients with moderate hypokalemia had significantly higher FT3(8.31 ± 9.07 pmol/L vs.6.15±6.09 pmol/L,P=0.034)and FT4(28.62 ± 31.05 pmol/L vs.21.45±19.06 pmol/L,P=0.036)levels.And patients with severe hypokalemia had higher FT3(8.71± 8.03 pmol/L vs.6.15±6.09 pmol/L,P=0.005),FT4(27.72±25.43 pmol/L vs.21.45± 19.06 pmol/L,P=0.043)and CO2CP(26.29 ± 6.39 mmol/L vs.24.77 ± 4.96 mmol/L,P=0.043)levels and lower TC(4.46 ± 1.46 mmol/L vs.4.86±1.58 mmol/L,P=0.014)and LDL-C levels(2.63 ± 0.96 mmol/L vs.2.95 ± 1.10 mmol/L,P=0.006)than patients with mild hypokalemia.Additionally,patients with severe hypokalemia had a higher proportion of males(73.38%vs.52.60%,P<0.001 and 73.38%vs.43.17%,P<0.001)and younger age(36.28±15.89y vs.44.20± 18.03,P<0.001 and 36.28 ±15.89y vs.46.46±17.43y,P<0.001)than the other two groups.3.Logistic regression analysis of factors for moderate to severe hypokalemiaIn logistic regression analysis,male(OR=2.059,P<0.001)was identified as risk factor for moderate to severe hypokalemia.Hyperthyroidism(OR=2.835,P=0.001),primary aldosteronism(OR=2.642,P=0.005),renal tubular acidosis(OR=4.817,P=0.001)and Gitelman's syndrome(ORF=6.420,P=0.023)had higher risks of moderate to severe hypokalemia than abnormal glucose metabolism.Summary and conclusions:1.Diabetes,hyperthyroidism and primary aldosteronism are common causes of hypokalemia.2.Male,hyperthyroidism,primary aldosteronism,renal tubular acidosis and Gitelman's syndrome are independent risk factors for moderate to severe hypokalemia. |
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