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The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.
Subject(s)
Humans , Transcription Factors/metabolism , Nuclear Proteins/metabolism , Histones , Cell Cycle Proteins/metabolism , Neoplasms/metabolism , Protein DomainsABSTRACT
Objective:To discuss the relationship between heart rate (HR) and heart rate differences (HRD) at different time points in head-up tilt test (HUTT) and the occurrence of postural tachycardia syndrome(POTS) in children and adolescents.Methods:A total of 217 children and adolescents diagnosed as POTS, who complained of syncope or presyncope, were chosen as POTS group (aged 6 to 16 years). During the same period, 73 healthy children and adolescents with matching gender and age were selected as control group.All subjects underwent HUTT from October 2000 to November 2019.Get HR (HR0, HR5, HR10) in baseline, HUTT 5 min and 10 min, HRD (HRD5, HRD10) of HR in HUTT 5 min and 10 min minus HR in baseline.Results:(1) HR5, HR10, HRD5, and HRD10 were higher in the POTS group than those in the control group( P<0.05). (2) Univariate Logistic regression: There was a correlation between HR5, HR10, HRD5, HRD10 and the risk of POTS( P<0.01). (3) Multivariable Logistic regression: For each additional unit of HRD5 and HRD10, the risk of POTS increased by 27% ( OR=1.27, 95% CI1.16 to 1.36) and 28% ( OR=1.28, 95% CI1.20 to 1.38). Conclusion:HR and HRD are related with the occurrence of POTS in children and adolescents, but HR and HRD at different time points of HUTT play the little role on the effect size of the occurrence of POTS.
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Objective:To investigate the relationship between body mass index (BMI) and response time of cardioinhibitory type vasovagal syncope (VVS-CI) in children.Methods:The clinical data of 56 children with syncope or pre-syncope were retrospectively analyzed and they visited specialist clinic for syncope and were diagnosed as VVS-CI in the Second Xiangya Hospital, Central South University from December 2012 to September 2019.Based on height and weight, BMI was calculated, and divided into low BMI group (35 cases) and normal BMI group (21 cases). Between the 2 groups, baseline heart rate, head-up tilt test (HUTT) positive response heart rate, baseline head-up tilt test (BHUT) positive response time, and sublingual nitroglycerin-provocated HUTT (SNHUT) positive response time were compared.The correlation between BMI and positive response time was analyzed.SPSS 22.0 software was applied for statistical analysis.Results:There were no significant differences in age, sex, duration of disease and number of syncope between the 2 groups (all P>0.05). No significant differences were found in baseline heart rate and positive response heart rate between the 2 groups [(78.5±15.3) times/min vs.(72.8±8.7) times/min, t=1.223, P=0.230; (44.0±13.9) times/min vs.(47.0±10.0) times/min, t=-0.664, P=0.511]. Compared with normal BMI group, BHUT positive patients/SNHUT positive patients were higher in low BMI group (27/8 cases vs.9/12 cases, χ2=4.839, P=0.027), and the positive response time of BHUT was shorter [(13.1±4.6) min vs.(23.7±9.5) min, t=-2.691, P=0.023]. There were no significant differences in SNHUT positive response time between the 2 groups ( P>0.05). Low BMI was correlated with BHUT positive response time ( r=0.750, P=0.005). Normal BMI was not associated with BHUT positive response time ( r=0.316, P=0.217). There was no correlation between low BMI and normal BMI and SNHUT positive response time ( r=0.177, P=0.431; r=0.021, P=0.940). Conclusions:Low BMI is positively correlated with BHUT positive response time of children with VVS-CI.The time it takes for syncope occurrence was shorter in children with low BMI than that in normal BMI.
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Objective:To investigate the value of rate-pressure product (RPP) in predicating the prognosis of postural tachycardia syndrome (POTS) in children.Methods:Fifty-three children (26 males and 27 females) aged 5 to 15 who had syncope of unknown reasons or presyncope and were diagnosed with POTS by head-up tilt test (HUTT) at the Children′s Syncope Specialist Clinic, the Second Xiangya Hospital, Central South University from April 2012 to May 2019 were selected as the POTS group.Thirty-eight children aged 5 to 16 (19 males and 19 females) who underwent medical examinations at the Children′s Health Specialist Clinic of the Second Xiangya Hospital, Central South University over the same period were enrolled as controls (control group). POTS children were followed up after intervention and they were divided into the response group ( n=40) and the non-response group ( n=13) according to the follow-up results.The products (RPP0, RPP5, RPP10) of the heart rate (HR0, HR5, HR10) and systolic blood pressure (SBP0, SBP5, SBP10) at baseline (HUTT 0 min), HUTT 5 min and HUTT 10 min were calculated.Statistical analysis was performed using SPSS 22.0 software and EmpowerStats software. Results:(1) There was no statistical difference in age and gender between the POTS group and the control group (all P> 0.05). (2) HR5 [(115.45±14.50) times/min vs.(95.79±13.89) times/min], HR10 [(120.57±16.13) times/min vs.(96.05±12.43) times/min], RPP5 (12 814.55±2 304.56 vs.10 371.42±1 910.20), and RPP10 (13 449.17±2 360.40 vs.10 523.18±1 771.48) in the POTS group were significantly higher than those in the control group( t=0.799, 7.842, 5.747, 6.446, all P<0.01). No statistical difference of HR0 and RPP0 was observed between the 2 groups (all P>0.05). (3) In the POTS group: HR5 [(98.73±12.43) times/min vs.(113.77±17.65) times/min], HR10 [(96.90±13.96) times/min vs.(119.08±13.52) times/min], RPP5 (11 125.45±1 952.35 vs.12 914.69±3 192.12) and RPP10 (10 819.58± 2 144.26 vs.13 375.46±2 807.01) in the response group were significantly lower than those in the non-response group( t=3.406, 5.012, 2.432, 3.455, all P<0.01). HR0 and RPP0 were no significantly different between the 2 groups(all P>0.05). (4) When SBP10<114 mmHg(1 mmHg= 0.133 kPa), the probability of response after POTS intervention increased by 10% with every 1 mmHg increase in SBP10, and there was a non-linear relationship between the 2 group ( P<0.05). (5) The receiver operating characteristic curve suggested that when RPP5 was 11 548.50, the sensitivity and specificity to predict the response after POTS intervention were 81.82% and 61.70%, respectively.When RPP10 was 10 988.00, the sensitivity and specificity were 77.78% and 86.21%, respectively. Conclusions:RPP is closely related to the intervention effect of POTS in children.RPP5 and RPP10 can predict the prognosis of POTS in children.There is a non-linear relationship between SBP10 and the intervention effect of POTS in children.
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Objective To discuss the relationship between body mass index(BMI)and flag_raising syncope ( PS)and micturition syncope(MS)in children and adolescents. Methods One hundred and six children and adoles_cents with PS or MS diagnosed at the Department of Dediatric Cardiovasology,Childrenˊs Medical Center,the Second Xiangya Hospital,Central South University from January 2003 to September 2017 were studied,including 51 males and 55 females,and their ages ranged from 5 to 18 years. There were 63 cases in the PS group(21 males and 42 females) and 43 cases in the MS group(30 males and 13 females). One hundred healthy children and adolescents including 50 males and 50 females who had routine healthy examinations at the hospital in the same period were selected as control subjects(healthy control group). Body length and body mass were measured,and BMI was calculated. Statistical inves_tigations were conducted with SDSS 22. 0 software. Results (1)The body mass and BMI in the PS group were lower than those in the MS group[(36. 33 ± 9. 85)kg vs.(42. 85 ± 12. 44)kg;(16. 56 ± 2. 41)kg∕m2 vs.(18. 48 ± 3. 04) kg∕m2],and the differences were statistically significant(F﹦7. 529,12. 411,all P〈0. 05). There was no difference in body length among the PS group,the MS group and the healthy control group[(146. 62 ± 12. 89)cm vs.(150. 79 ± 12. 78)cm vs.( 149. 75 ± 16. 02 )cm,F ﹦1. 314,P 〉0. 05 ]. No differences were found in age,frequency,body length,body mass and BMI between the PS syncope group and the MS group with different genders(all P〉0. 05).(2) The number of BMI_underweight children increased in the PS group(82. 53%,52∕63 cases)compared with that of the MS group(58. 14%,25∕43 cases)and that of the healthy control group( 52. 00%,52∕100 cases),and the difference was statistically significant(χ2 ﹦14. 556,P〈0. 01).(3)The positive rate by head_up tilt test(HUTT)was 72. 64%(77∕104 cases),and HUTT of the PS group was higher than that of the MS group[82. 53%(52∕63 cases)vs. 58. 14%(25∕43 cases)],and there was a significant difference statistically(χ2 ﹦7. 656,P〈0. 01). Conclusions Low BMI is prone to PS in children and adolescents.