OBJECTIVETo study the expression of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in children with tetralogy of Fallot (TOF), and to investigate the role of histone acetylation and acetylation-related enzymes in the pathogenesis of TOF.

METHODSMyocardial tissue samples in the TOF group were obtained from 46 children with TOF who underwent radical operation, and myocardial tissue samples in the control group were obtained from 16 children who suffered accidental deaths and had no cardiac anomalies as shown by autopsy. The acetylation of H3K9, H3K18 and H3K27 was evaluated by immunohistochemistry. The mRNA expression of HATs and HDACs in the myocardium was measured by real-time PCR. The correlation between mRNA expression of HATs and HDACs and histone acetylation was analyzed.

RESULTSCompared with the control group, the TOF group showed significantly increased acetylation of H3K9 (P=0.0165) and significantly decreased acetylation of H3K18 (P=0.0048) and H3K27 (P=0.0084). As to 4 HATs and 6 HDACs, the mRNA expression of EP300 and CBP was significantly higher in the TOF group than in the control group (P=0.025; P=0.017), and there was no significant difference in the mRNA expression of other HATs and HDACs between the two groups. The correlation analysis revealed a positive correlation between H3K9 acetylation and mRNA expression of EP300 (r=0.71, P<0.01) and CBP (r=0.72, P<0.01).

CONCLUSIONSUpregulated mRNA expression of EP300 and CBP may be associated with increased H3K9 acetylation, suggesting that EP300 and CBP might affect cardiac development by regulating H3K9 acetylation.

Acetylation ; E1A-Associated p300 Protein ; genetics ; Female ; Histone Acetyltransferases ; genetics ; Histone Deacetylases ; genetics ; Histones ; metabolism ; Humans ; Infant ; Male ; Myocardium ; metabolism ; Peptide Fragments ; genetics ; RNA, Messenger ; analysis ; Sialoglycoproteins ; genetics ; Tetralogy of Fallot ; metabolism

Objective To explore the value of dual-phase contrast-enhancement multislice computed tomography (MSCT) in the assessment of acute myocardial infarction volume and perfusion in porcine models. Methods The distal left anterior descending coronary arteries of 5 pigs were balloon-occluded for 90 min and followed by reperfusion. MSCT was performed 1 min (early phase) and 5 min (delayed phase) after administration bolus of 100 mL of iodinated contrast material 30 min after reperfusion. On the same day, hearts were excised, sectioned in 8 mm short-axis slices, and stained with TTC. Infarction volume was defined as the sum of the hyper-enhanced area and surrounding hypo-enhanced area in all slices on delay enhanced phase of MSCT and the TTC-negative area on TTC staining slices. Infarction volume was expressed as percentage of total slice volume. Results Acute infarction detected by MSCT was characterized by early myocardial perfasion defects in the early phase of the contrast bolus (early defects) with surrounding residual defects and late enhancement observed in the late phase. Mean CT attenuation value of early defects was significantly different from CT attenuation value of remote myocardium [(213±55)HU vs (304±30)HU](P < 0.05), CT attenuation values of residual defects and late enhancement were also significantly different from those of remote myocardium [(360±75) HU vs (90±37) HU and (152±23) HU vs (190±37) HU, repectively](P < 0.01, P < 0.05). The mean infarction volume was (8.9± 1.0)% on MSCT and (9.2±1.4)% on TTC pathology images. The infarction volume assessed by MSCT compared well with TTC staining slices. Conclusion Acute reperfused myocardial infarction zone has specific enhancement pattens different to remote normal zone on dual phase MDCT, which is in good agreement with in vivo Trc pathology in the assessment of acute reperfused myocardial infarction shortly offer reperfusion.

OBJECTIVETo investigate the relationship between the genotypes of hepatitis B virus and the clinical and liver pathological features of patients with chronic hepatitis in the Zhoushan Islands.

METHODSOne hundred eighty HBV DNA positive chronic hepatitis patients with HBV markers were enrolled in this study. They were at least second generation Zhoushan Island residents. One hundred forty-seven of them were males and 33 were females with an average age of 39.0+/-11.3. Among the 180 patients, 17 had ASC, 57 had mild CHB, 48 moderate CHB, 9 severe CHB, 6 SHB, 39 LC, and 4 had HCC. The genotypes of their serum HBV were detected by using PCR integrated with Tagman MGB probe technology, and their serum HBV markers, HBV DNA and liver functions were also examined. Out of 180 patients, 129 accepted a liver biopsy. A pathological evaluation was then performed.

RESULTSHBVs of genotype C, 135 cases (75.0%), of B, 40 cases (22.2%), and of B+C, 5 cases (2.8%) were found among these 180 patients. No genotype A or D HBV were found. The proportions of genotype C virus were 7/17, 86/114, 34/39, 6/6 in ASC, CHB, LC and SHB patients. In the hepatocellular carcinoma patients, there were 2 each of genotype B and C. Among the 99 patients with genotype C HBV, 84 cases (84.8%) showed moderate and severe inflammation histologically in their livers and among the 30 patients with B, 7 cases (23.3%) showed moderate to severe inflammation in their livers (z = 6.47, P less than 0.01). The proportion of genotype C HBV was significantly different from that of genotype B HBV in those that showed moderate and severe (S3-4) liver fibrosis. In patients infected with genotype C HBV who had moderate and severe liver pathological changes, their clinical manifestations reflected better the histological alterations of their livers.

CONCLUSIONGenotypes C, B and B+C HBV were found in CHB patients in the Zhoushan Islands of China, and type C was the predominant one. The liver pathological damage level of genotype C HBV infected patients is more serious than that of genotype B.

Adult ; China ; epidemiology ; DNA, Viral ; genetics ; Female ; Genome, Viral ; Genotype ; Hepatitis B virus ; classification ; genetics ; Hepatitis B, Chronic ; epidemiology ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged

Coronary Angiography ; Coronary Vessel Anomalies ; diagnostic imaging ; therapy ; Embolization, Therapeutic ; methods ; Fistula ; congenital ; diagnostic imaging ; therapy ; Heart Ventricles ; abnormalities ; diagnostic imaging ; Humans ; Male ; Middle Aged

BACKGROUNDMeniere's disease is a unique, progressive disease of the inner ear. The complex manifestation presents diagnostic challenges. The cochlear symptoms often present before vertigo and tend to be ignored. This study aimed to analyze the characteristics of cochlear symptoms and functions associated with Meniere's disease to investigate the regularity of the development of this disorder.

METHODSOne-hundred fifteen patients who were diagnosed with definite unilateral Meniere's disease at the Hearing and Vestibular Clinic of the Department of Otorhinolaryngology of Beijing Tongren Hospital from August 2013 to November 2015 were recruited in this retrospective study. Initial symptoms, duration from initial symptoms to the diagnosis, hearing thresholds, audiogram patterns, and caloric test results were collected and analyzed for each patient. Data were analyzed using SPSS 13.0 statistical software by Spearman's correlation, Kruskal-Wallis H test, Chi-square test, and Fisher's exact test.

RESULTSThe average hearing threshold of these patients was 45.24 ± 18.40 dB HL. A majority of the patients (55.65%) were in Stage 3. The initial presentation of the disorder in 58 cases (50.43%) comprised only cochlear symptoms without vertigo. A weak, positive correlation was found between the degree of hearing loss and duration of the disease from initial symptoms to the diagnosis (rs = 0.288, P = 0.002). Upward-sloping, inverted "V," downward-sloping, and flat pattern were the main audiometric patterns observed with a distinctive distribution between stages (P < 0.001). Based on the configurations of audiograms, the audiometric patterns had a weak correlation to the duration (rs = 0.269, P = 0.004), and there was a tendency of duration to rising from upward-sloping, inverted "V", downward-sloping to flat pattern. (H = 10.024, P = 0.018). Frequencies of tinnitus in 56 patients (64.4%) were at the lowest points of the audiograms, i.e., the frequencies of the poorest hearing threshold. The patients at an advanced stage (Stage 3 [56] and Stage 4 [73]) exhibited a significantly higher abnormality of canal paresis than those at the earlier stages (Stage 1 [23] and Stage 2 [42]) (χ2 = 5.973, P = 0.015).

CONCLUSIONSPatients with definite Meniere's disease always have a moderate to severe sensorineural hearing loss before diagnosis. Cochlear symptoms are the most common initial presentation. With the progression of the duration, the hearing impairment becomes more severe and the distribution of the audiometric pattern is distinctive between stages.

Adolescent ; Adult ; Aged ; Caloric Tests ; Cochlea ; physiopathology ; Female ; Hearing Loss ; diagnosis ; physiopathology ; Humans ; Male ; Meniere Disease ; diagnosis ; physiopathology ; Middle Aged ; Retrospective Studies ; Tinnitus ; diagnosis ; physiopathology ; Vertigo ; diagnosis ; physiopathology ; Young Adult

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies. Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout. Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population. Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population. Clinical Trial Identifier NCT00856544 and NCT00413699.
Administration, Oral ; Adult ; Aged ; Arthritis, Rheumatoid ; drug therapy ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Middle Aged ; Piperidines ; adverse effects ; therapeutic use ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use ; Pyrroles ; adverse effects ; therapeutic use ; Surveys and Questionnaires ; Young Adult

OBJECTIVE: To evaluate the association between serum uric acid (SUA) and kidney function decline. METHODS: Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis. The kidney function decline was defined as an annual estimated glomerular filtration rate (eGFR) decrease by > 3 mL/min per 1.73 m ². Multivariable logistic regression was applied to determine the association between SUA and kidney function decline. The shape of the association was investigated by restricted cubic splines. RESULTS: A total of 7,346 participants were included, of which 1,004 individuals (13.67%) developed kidney function decline during the follow-up of 4 years. A significant dose-response relation was recorded between SUA and the kidney function decline ( OR 1.14, 95% CI 1.03-1.27), as the risk of kidney function decline increased by 14% per 1 mg/dL increase in SUA. In the subgroup analyses, such a relation was only recorded among women ( OR 1.22, 95% CI 1.03-1.45), those aged < 60 years ( OR 1.22, 95% CI 1.05-1.42), and those without hypertension and without diabetes ( OR 1.22, 95% CI 1.06-1.41). Although the dose-response relation was not observed in men, the high level of SUA was related to kidney function decline ( OR 1.83, 95% CI 1.05-3.17). The restricted cubic spline analysis indicated that SUA > 5 mg/dL was associated with a significantly higher risk of kidney function decline. CONCLUSION The SUA level was associated with kidney function decline. An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.
Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; East Asian People ; Glomerular Filtration Rate ; Kidney/physiopathology* ; Longitudinal Studies ; Risk Factors ; Uric Acid/blood*