The mechanisms, regulations, and functions of histone lysine crotonylation.

Histone lysine crotonylation (Kcr) is a new acylation modification first discovered in 2011, which has important biological significance for gene expression, cell development, and disease treatment. In the past over ten years, numerous signs of progress have been made in the research on the biochemistry of Kcr modification, especially a series of Kcr modification-related "reader", "eraser", and "writer" enzyme systems are identified. The physiological function of crotonylation and its correlation with development, heredity, and spermatogenesis have been paid more and more attention. However, the development of disease is usually associated with abnormal Kcr modification. In this review, we summarized the identification of crotonylation modification, Kcr-related enzyme system, biological functions, and diseases caused by abnormal Kcr. This knowledge supplies a theoretical basis for further exploring the function of crotonylation in the future.

The prognostic value of CT-derived fractional flow reserve in coronary artery bypass graft: a retrospective multicenter study.

OBJECTIVES: To investigate the predictive value of CT-derived fractional flow reserve (FFRCT) in anastomosis occlusion after coronary artery bypass graft (CABG) surgery. METHODS: Patients undergoing CABG with both pre- and post-operative coronary computed tomographic angiography (CCTA) were retrospectively included. Preoperative CCTA studies were used to evaluate anatomical and FFRCT information of target vessels. A diameter stenosis (DS) ≥ 70% or left main > 50% was considered to be anatomically severe, while FFRCT value ≤ 0.80 be functionally significant. The primary endpoint was anastomosis occlusion evaluated on post-operative CCTA during follow-up. Predictors of anastomosis occlusion were assessed by the multivariate binary logistic regression with generalized estimating equations. RESULTS: A total of 270 anastomoses were identified in 88 enrolled patients. Forty-one anastomoses from 30 patients exhibited occlusion during a follow-up of 15.3 months after CABG. The occluded group had significantly increased prevalence of non-severe DS (58.5% vs. 40.2%; p = 0.023) and non-significant FFRCT (48.8% vs. 10.0%; p < 0.001). Multivariable analysis indicated FFRCT ≤ 0.80 (odds ratio [OR]: 0.10, 95% CI: 0.03-0.33; p < 0.001) and older age (OR: 0.92, 95% CI: 0.87-0.97; p = 0.001) were predictors for bypass patency during follow-up, while myocardial infarction history and anastomosis to a local lesion or bifurcation (all p value < 0.05) were predictors of occlusion. Adding FFRCT into the model based on the clinical and anatomical predictors had an improved AUC of 0.848 (p = 0.005). CONCLUSIONS: FFRCT ≤ 0.80 was associated with a significant risk reduction of anastomosis occlusion after CABG. Preoperative judgment of the hemodynamic significance may improve the CABG surgery strategy and reduce graft failure. KEY POINTS: • FFRCT ≤ 0.80 was associated with a significant risk reduction of anastomosis occlusion after CABG. • The addition of FFRCT into the integrated model including clinical (age and history of myocardial infarction) and anatomical CCTA indicators (local lesion and bifurcation) significantly improved the model performance with an AUC of 0.848 (p = 0.005). • Preoperative judgment of the hemodynamic significance may help improve the decision-making and surgery planning in patients indicated for CABG and significantly reduce graft failure, without an extra radiation exposure and risk of invasive procedure.

Optimal Measurement Sites of Coronary-Computed Tomography Angiography-derived Fractional Flow Reserve: The Insight From China CT-FFR Study.

OBJECTIVES: To investigate the optimal measurement site of coronary-computed tomography angiography-derived fractional flow reserve (FFR CT ) for the assessment of coronary artery disease (CAD) in the whole clinical routine practice. MATERIALS AND METHODS: This retrospective multicenter study included 396 CAD patients who underwent coronary-computed tomography angiography, FFR CT , and invasive FFR. FFR CT was measured at 1 cm (FFR CT -1 cm), 2 cm (FFR CT -2 cm), 3 cm (FFR CT -3 cm), and 4 cm (FFR CT -4 cm) distal to coronary stenosis, respectively. FFR CT and invasive FFR ≤0.80 were defined as lesion-specific ischemia. The diagnostic performance of FFR CT to detect ischemia was obtained using invasive FFR as the reference standard. Reduced invasive coronary angiography rate and revascularization efficiency were calculated. After a median follow-up of 35 months in 267 patients for major adverse cardiovascular events (MACE), Cox hazard proportional models were performed with FFR CT values at each measurement site. RESULTS: For discriminating lesion-specific ischemia, the areas under the curve of FFR CT -1 cm (0.91) as well as FFR CT -2 cm (0.91) were higher than those of FFR CT -3 cm (0.89) and FFR CT -4 cm (0.88), respectively (all P <0.05). The higher reduced invasive coronary angiography rate (81.6%) was found at FFR CT -1 cm than FFR CT -2 cm (81.6% vs. 62.6%, P <0.05). Revascularization efficiency did not differ between FFR CT -1 cm and FFR CT -2 cm (80.8% vs. 65.5%, P =0.019). In 12.4% (33/267) MACE occurred and only values of FFR CT -2 cm were independently predictive of MACE (hazard ratio: 0.957 [95% CI: 0.925-0.989]; P =0.010). CONCLUSIONS: This study indicates FFR CT -2 cm is the optimal measurement site with superior diagnostic performance and independent prognostic role.

Relationship of lipoprotein-associated phospholipase A2(Lp-PLA2) and periprocedural myocardial injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is one of the dominant methods for revascularization in patients with coronary heart disease (CHD). However, periprocedural myocardial injury (PMI) is a frequent complication following PCI and is known to be a predictor of postprocedural cardiovascular morbidity and mortality. Although several studies try to identify serum markers to predict the PMI, there is a little information about the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) as a predictor of PMI. Therefore, we aimed to investigate the relationship of Lp-PLA2 levels and PMI in patients undergoing elective PCI. METHODS: This study included 265 consecutive patients with normal preprocedural cardiac troponin T(cTNT) who received elective PCI. The samples for cTNT were collected at 8, 16, and 24 h after PCI to assess perioperative myocardial injury. The Lp-PLA2 and other serum lipid parameters were measured after 12 fasting hours before PCI. RESULTS: The data suggested that the patients with preprocedural high Lp-PLA2 were strongly and independently correlated with the risk of PMI. Pearson correlation analysis showed that preprocedural Lp-PLA2 was significantly positively correlated with postprocedural cTnT elevation (r = 0.694, p < 0.05). Binary logistic regression analysis was used to analyze the risk factors of PMI, we found that Lp-PLA2 was independent risk factor for postprocedural cTnT elevation. The area under Receiver Operating Characteristic curve of Lp-PLA2 was 0.757 (95%CI 0.692 ~ 0.821, p < 0.001), the best cut-off point was 185 ng/ml, sensitivity and specificity were 65.33% and 76.32%. CONCLUSION: Our study demonstrated that preprocedural Lp-PLA2 was associated with postprocedural cTnT elevation and was the independent risk factor of PMI.

Exploring the relationship of peripheral total bilirubin, red blood cell, and hemoglobin with blood pressure during childhood and adolescence / Explorando a relação entre os níveis periféricos de bilirrubina total, glóbulos vermelhos e hemoglobina e a pressão arterial na infância e adolescência

Abstract Objective: Total bilirubin is beneficial for protecting cardiovascular diseases in adults. The authors aimed to investigate the association of total bilirubin, red blood cell, and hemoglobin levels with the prevalence of high blood pressure in children and adolescents. Methods: A total of 3776 students (aged from 6 to 16 years old) were examined using cluster sampling. Pre-high blood pressure and high blood pressure were respectively defined as the point of 90th and 95th percentiles based on the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Both systolic and diastolic blood pressure were standardized into z-scores. Results: Peripheral total bilirubin, red blood cell and hemoglobin levels were significantly correlated with age, and also varied with gender. Peripheral total bilirubin was negatively correlated with systolic blood pressure in 6- and 9-year-old boys, whilst positively correlated with diastolic blood pressure in the 12-year-old boys and 13- to 15-year-old girls (p < 0.05). Higher levels of red blood cell and hemoglobin were observed in pre-high blood pressure and high blood pressure students when compared with their normotensive peers (p < 0.01). The increases in red blood cell and hemoglobin were significantly associated with high blood pressure after adjusting for confounding factors. The ORs (95% CI) of each of the increases were 2.44 (1.52-3.92) and 1.04 (1.03-1.06), respectively. No statistical association between total bilirubin and high blood pressure was observed (p > 0.05). Conclusion: Total bilirubin could be weakly correlated with both systolic and diastolic blood pressure, as correlations varied with age and gender in children and adolescents; in turn, the increased levels of red blood cell and hemoglobin are proposed to be positively associated with the prevalence of high blood pressure.

Resumo Objetivo: A bilirrubina total é benéfica para proteger contra doenças cardiovasculares em adultos. Nosso objetivo foi investigar a associação dos níveis de bilirrubina total, glóbulos vermelhos e hemoglobina com a prevalência de pressão arterial elevada em crianças e adolescentes. Métodos: Um total de 3.776 estudantes (com idade entre 6-16 anos) foram examinados utilizando uma amostra em blocos. A pressão arterial elevada anterior e a pressão arterial elevada foram definidas como o 90° e 95° percentil, respectivamente, com base nos critérios do Quarto Relatório sobre Diagnóstico, Avaliação e Tratamento da Pressão Arterial elevada em Crianças e Adolescentes. A pressão arterial sistólica e pressão arterial diastólica foram padronizadas no escore z. Resultados: Os níveis periféricos de bilirrubina total, glóbulos vermelhos e hemoglobina foram significativamente correlacionados à idade, que também variou de acordo com o sexo. A bilirrubina total periférica apresentou uma correlação negativa com a pressão arterial sistólica em meninos com 6 e 9 anos, ao passo que apresentou uma correlação positiva com a pressão arterial diastólica em meninos de 12 anos e meninas de 13 a 15 anos (p < 0,05). Foram observados níveis mais elevados de glóbulos vermelhos e hemoglobina em estudantes com pressão arterial elevada anterior e pressão arterial elevada em comparação a indivíduos normotensos (p < 0,01). Os aumentos de glóbulos vermelhos e hemoglobina tiveram uma associação significativa com a pressão arterial elevada após ajuste dos fatores de confusão. As RC (IC de 95%) de cada um dos aumentos foram 2,44 (1,52-3,92) e 1,04 (1,03-1,06) respectivamente. Não foi observada nenhuma associação estatística entre o nível de bilirrubina total e a pressão arterial elevada (p > 0,05). Conclusão: A bilirrubina total pode ter correlações fracas com a pressão arterial sistólica e a pressão arterial diastólica, variando de acordo com a idade e o sexo em crianças e adolescentes, enquanto isso, propõe-se que o aumento dos níveis de glóbulos vermelhos e hemoglobina está positivamente associado à prevalência de pressão arterial elevada.

Enhanced immune responses and effectiveness of refined outer membrane protein vaccines against Vibrio harveyi in orange-spotted grouper (Epinephelus coioides).

Vibriosis is a severe infection occurring in many commercially important marine fish species. In this study, vaccines containing Vibrio harveyi recombinant outer membrane protein K (rOmpK), outer membrane protein U (rOmpU) and rOmpK-OmpU fusion protein in addition to the metabolizable MontanideTM ISA 763 A VG adjuvant were developed and evaluated in the orange-spotted grouper. The results indicate that recombinant V. harveyi protein-based vaccines resulted in a remarkably higher expression of IL-1ß and IL-8 at 24 hr, and greater antibody production, as early as 2 weeks postimmunization. Notably, enhanced immune responses and significant protective efficacy against V. harveyi infections were observed in the fusion protein vaccine-injected fishes with relative per cent survival value of 81.8%. Additionally, the rOmpK-OmpU antisera presented a high bactericidal effect on not only V. harveyi, but also Vibrio parahaermolyticus and Vibrio alginolyticus. Our results demonstrated that the fusion protein rOmpK-OmpU was an effective vaccine candidate that exhibited potentially great versatility for controlling vibrio infections.

Exploring the relationship of peripheral total bilirubin, red blood cell, and hemoglobin with blood pressure during childhood and adolescence.

OBJECTIVE: Total bilirubin is beneficial for protecting cardiovascular diseases in adults. The authors aimed to investigate the association of total bilirubin, red blood cell, and hemoglobin levels with the prevalence of high blood pressure in children and adolescents. METHODS: A total of 3776 students (aged from 6 to 16 years old) were examined using cluster sampling. Pre-high blood pressure and high blood pressure were respectively defined as the point of 90th and 95th percentiles based on the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Both systolic and diastolic blood pressure were standardized into z-scores. RESULTS: Peripheral total bilirubin, red blood cell and hemoglobin levels were significantly correlated with age, and also varied with gender. Peripheral total bilirubin was negatively correlated with systolic blood pressure in 6- and 9-year-old boys, whilst positively correlated with diastolic blood pressure in the 12-year-old boys and 13- to 15-year-old girls (p<0.05). Higher levels of red blood cell and hemoglobin were observed in pre-high blood pressure and high blood pressure students when compared with their normotensive peers (p<0.01). The increases in red blood cell and hemoglobin were significantly associated with high blood pressure after adjusting for confounding factors. The ORs (95% CI) of each of the increases were 2.44 (1.52-3.92) and 1.04 (1.03-1.06), respectively. No statistical association between total bilirubin and high blood pressure was observed (p>0.05). CONCLUSION: Total bilirubin could be weakly correlated with both systolic and diastolic blood pressure, as correlations varied with age and gender in children and adolescents; in turn, the increased levels of red blood cell and hemoglobin are proposed to be positively associated with the prevalence of high blood pressure.

Efficacy of a formalin-inactivated vaccine against Streptococcus iniae infection in the farmed grouper Epinephelus coioides by intraperitoneal immunization.

Vaccination is the most effective means of preventing infectious diseases; however, few vaccines are effective against Streptococcus iniae (S. iniae) in grouper. This work presents an efficacious and safe vaccine against S. iniae infections in the grouper Epinephelus coioides. The vaccine candidate was the S. iniae GSI-310 strain. The vaccination was administered by intraperitoneal injection, and consisted of formalin-inactivated antigens combined with an AS-F or ISA763A adjuvant. Peripheral blood samples were collected for RT-qPCR and phagocytosis and agglutination assays. Our results indicated that immunoglobulin M (igm) was maximally expressed in the two vaccinated groups at 3 months post-secondary vaccination (PSV). A significant upregulation of mRNA expression for interleukin-1ß (il-1ß) and tumor necrosis factor-α (tnf-α) was also observed in fish treated with antigens combined with ISA763A, which peaked at 3 months PSV. In fish treated with antigens combined with AS-F, il-1ß and tnf-α expression peaked at 14 days post-primary vaccination (PPV). Phagocytic activity and index increased significantly in the two vaccinated groups. Furthermore, fish in the two vaccinated groups exhibited significantly elevated agglutination titers compared to fish in the control group, in which almost no agglutination reaction was detected. In the efficacy test, the vaccinated and control groupers were treated with S. iniae at 1, 3, and 6 months PSV. The relative percentage survival (RPS) values of antigens with AS-F and antigens with ISA763A were both 100% at 1 and 3 months PSV; at 6 months PSV, the RPS values for these groups were 100% and 97.7%, respectively. Furthermore, the level of protection observed in the field trial closely resembled that achieved on a laboratory scale. Therefore, the proposed vaccine mixed with AS-F or ISA763A improved immune responses and provided safe and long-lasting protection in farmed groupers.

[An association study between transforming growth factor-ß1 receptor 2 gene polymorphisms and essential hypertension].

OBJECTIVE: To evaluate the association between two single nucleotide polymorphisms located in the promoter of transforming growth factor-ß1 receptor 2 (TGFBR2) gene and hypertension in Han Chinese population. METHODS: The subjects were recruited from the population of cluster sampling survey for essential hypertension (EH) in two townships of Yixing city, Jiangsu province in 2009. Overall, 2012 patients with hypertension and 2116 age (± 2 years) and sex-matched unrelated controls were selected. Epidemiological data, physical measurements results and serum glucose and lipid biomarker were collected and detected. Linkage disequilibrium (LD) analysis were applied and two tagging single nucleotide polymorphisms (tagSNP) in 5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/G) were selected for genotyping and analyzing for the association with hypertension. RESULTS: The frequencies of AA, AG, GG in case and control of rs6785358 were 1455 (72.3%), 517 (25.7%), 40 (2.0%) and 1582 (74.8%), 490 (23.2%), 43 (2.0%) respectively, and CC, CG, GG of rs764522 were 1524 (75.7%), 464 (23.1%), 24 (1.2%) and 1654 (78.2%), 436 (20.6%), 26 (1.2%) respectively. SNP rs764522 was significantly associated with EH and OR (95%CI) were 1.17 (1.01 - 1.36) (P < 0.05) in dominant model after adjustment for confounding factors such as age, sex, glucose, lipids, smoking and alcohol drinking. Further stratification analysis by age, sex, smoking and alcohol drinking indicated that individuals carrying G allele (CG/GG genotype) of SNP rs764522 had higher susceptibility to EH than CC genotype (OR = 1.21, 95%CI: 1.01 - 1.45) (P < 0.05) in ≥ 55 years group. No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs6785358 between cases and controls (P > 0.05). Haplotype analysis showed that no significant frequency difference of haplotype structured by rs6785358 and rs764522 was found between cases and controls (P > 0.05), and no significant blood pressure change was found between genotype variations of rs6785358 and rs764522 (P > 0.05). CONCLUSION: SNP rs764522 of TGFBR2 gene is associated with increased risk of EH in elderly Han Chinese population.

[The correlation between brain natriuretic peptide and invasive hemodynamic parameters and their value in prognosis of patients with noncardiac shock].

OBJECTIVE: To examine the correlation between the plasma level of brain natriuretic peptide (BNP) and the hemodynamic parameters collected through Swan-Ganz flowing balloon catheter procedure in patients with noncardiac shock, in order to evaluate the potential for BNP to be used as prognostic indicator. METHODS: The plasma BNP and invasive hemodynamic parameters data [central venous pressure (CVP), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), and cardiac output (CO)] were collected from 21 noncardiac shock patients received Swan-Ganz catheterization throughout a continuous surveillance for 3 days. The BNP, CVP, PAP, PCWP, CO in survivors (n = 8) and non-survivors (n = 13) were compared and the correlation between the value of BNP and the invasive hemodynamic parameters were analyzed using multiple regression. RESULTS: The mean value of BNP (ng/L) was significantly higher in non-survivors (708.06 ± 242.58 vs. 317.05 ± 140.21, P < 0.05). In day 1, no significant difference was found in any hemodynamic parameters between non-survivors and survivors. But in day 3, the non-survivors were found to have significantly higher CVP (mm Hg, 1 mm Hg = 0.133 kPa: 13.64 ± 4.00 vs. 9.92 ± 1.26, P < 0.05) and lower CO (L/min: 4.61 ± 2.06 vs. 6.95 ± 1.28, P < 0.05). The differences in PAP (mm Hg: 20.84 ± 8.48 vs. 16.82 ± 4.97) and PCWP (mm Hg: 13.60 ± 5.71 vs. 12.72 ± 4.98) remained insignificant (both P > 0.05) between the two groups. The correlation between BNP and the invasive hemodynamic parameters was modest there was no correlation between BNP and CVP, PAP, PCWP, CO (r = 0.157, 0.306, 0.229, -0.269, P = 0.16, 0.25, 0.09, 0.12). CONCLUSIONS: In patients with shock, both plasma BNP and invasive hemodynamic examination showed certain prognostic value. But in noncardiac shock cases, the increased BNP did not correlate with heart function, therefore it could not replace the Swan-Ganz catheter data to guide the treatment in these patients.

Spatial and seasonal characterization of net primary productivity and climate variables in southeastern China using MODIS data.

We developed a sophisticated method to depict the spatial and seasonal characterization of net primary productivity (NPP) and climate variables. The role of climate variability in the seasonal variation of NPP exerts delayed and continuous effects. This study expands on this by mapping the seasonal characterization of NPP and climate variables from space using geographic information system (GIS) technology at the pixel level. Our approach was developed in southeastern China using moderate-resolution imaging spectroradiometer (MODIS) data. The results showed that air temperature, precipitation and sunshine percentage contributed significantly to seasonal variation of NPP. In the northern portion of the study area, a significant positive 32-d lagged correlation was observed between seasonal variation of NPP and climate (P<0.01), and the influences of changing climate on NPP lasted for 48 d or 64 d. In central southeastern China, NPP showed 16-d, 48-d, and 96-d lagged correlation with air temperature, precipitation, and sunshine percentage, respectively (P<0.01); the influences of air temperature and precipitation on NPP lasted for 48 d or 64 d, while sunshine influence on NPP only persisted for 16 d. Due to complex topography and vegetation distribution in the southern part of the study region, the spatial patterns of vegetation-climate relationship became complicated and diversiform, especially for precipitation influences on NPP. In the northern part of the study area, all vegetation NPP had an almost similar response to seasonal variation of air temperature except for broad crops. The impacts of seasonal variation of precipitation and sunshine on broad and cereal crop NPP were slightly different from other vegetation NPP.

Application of jejunum with vascular pedicle in reconstruction of the digestive tract.

OBJECTIVE: To reconstruct the digestive tract using the jejunum with vascular pedicle after esophagectomy or gastrectomy, and observe the therapeutic effects and the patients' quality of life after the operation. METHODS: This study included a total of 25 patients, 10 of whom received proximal subtotal gastrectomy followed by reconstruction of the digestive tract with P-shaped jejunum for anastomosis of the esophagus and the residual stomach, 15 had total gastrectomy and anastomosis of the P-shaped jejunum with the esophagus inferior to the arch of aorta, with another 2 having total gastrectomy and the anastomosis superior to the arch of aorta. The pH value of the esophagus was tested, barium meal and gastroscopy were carried out 3 months after the operations, and the patients' quality of life assessed. RESULTS: Anastomotic leakage or infections in the thoracic or abdominal cavity occurred in none of the patients. All the patients had no postoperative difficulty in eating cooked rice, and were free of reflux esophagitis and burning sensation in the chest. The pH value of the esophagus was 5.5-6.6. Eight patients survived for more than 5 years. CONCLUSIONS: The effects of digestive tract reconstruction using the jejunum with vascular pedicle after esophagectomy or gastrectomy are satisfactory, especially in patients with esophageal cancer in the lower section or cardia cancer. This operation gives rise to low rate of operative complications, and insures good quality of life of the patients.