The potential of herbal drugs to treat heart failure:The roles of Sirt1/AMPK

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

Value of N-Terminal Pro B-Type Natriuretic Peptide,High-Sensitivity C-Reactive Protein,and Homocysteine Levels in Predicting Cardiovascular Events in Chronic Heart Failure Patients After Discharge

Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients with chronic heart failure(CHF).Methods:A total of 63 patients with CHF admitted to our hospital between June 2019 and July 2021 were selected.Their NT-proBNP,hs-CRP,and Hcy levels were detected at discharge,and a 12-month follow-up was done after their discharge to collect clinical data.The collected data were inclusive of data from 21 CHF patients with cardiovascular disease and 42 CHF patients without cardiovascular disease.The effect of NT-proBNP,hs-CRP,and Hcy levels on the occurrence of CV was analyzed.Results:The levels of NT-proBNP,hs-CRP,and Hcy in the group with cardiovascular disease were significantly higher than those in the group without cardiovascular disease(P<0.05);the levels of serum NT-proBNP,hs-CRP,and Hcy at discharge had certain value in predicting short-term CV in CHF patients(P<0.05).Conclusion:NT-proBNP,hs-CRP,and Hcy levels can be used to predict CV in CHF patients,thus having clinical application value.

Role of Heart-Type Fatty Acid Binding Protein in Early Detection of Acute Myocardial Infarction in Comparison with cTnI, CK-MB and Myoglobin

Heart fatty acid-binding protein (H-FABP) is supposed to be the most sensitive biomarker of early acute myocardial infarction (AMI). To evaluate the diagnostic value of H-FABP for AMI in the early stage, the plasma levels of H-FABP were measured by sandwich ELISA in 93 patients with suspected AMI at admission within 6 h after onset of chest pain and 69 normal healthy subjects. The plasma concentrations of cardiac troponin-I (cTnI), creatine kinase-MB (CK-MB) and myoglobin (Mb) were assayed at the same time by using corpuscle chemiluminescence for those patients. The patients were classified as AMI group (n=32) and non-AMI group (n=61) retrospectively. The diagnostic validity was evaluated in terms of sensitivity, specificity and receiver operating characteristic (ROC) curve analysis. The results showed the cutoff value of H-FABP for AMI was 16.8 ng/ml, and its diagnostic sensitivity for AMI was 64.29 % within 3 h and 84.38 % within 6 h after onset of chest pain, and the diagnostic specificity for non-AMI was 100 % within 3 h and 91.8 % within 6 h. H-FABP had higher sensitivity than that of cTnI and CK-MB at all time points (P<0.05), whereas there was no significant difference in specificity among the four markers. But the area under the ROC curve of H-FABP was significantly greater than that of cTnI, CK-MB and Mb within 3 h. These results revealed that H-FABP possessed high diagnostic sensitivity and specificity for AMI in early stage, especially within 3 h after onset of persistent angina pectoris. In conclusion, H-FABP can be used as a sensitive marker for AMI in the early stage.

H pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients with coronary heart disease

AIM: To determine the overall prevalence of H pylori and CagA positive H pylori infection and the prevalence of other bacterial and viral causes of chronic infection in patients with coronary heart disease (CHD), and the potential role of anti-heat-shock protein 60 (Hsp60) anti- body response to these proteins in increasing the risk of CHD development. METHODS: Eighty patients with CHD and 160 controls were employed. We also compared the levels of anti- heat-shock protein 60 (Hsp60) antibodies in the two groups. The H pylori infection and the CagA status were determined serologically, using commercially available enzyme-linked immunosorbent assays (ELISA), and a Western blotting method developed in our laboratory. Systemic antibodies to Hsp60 were determined by a sandwich ELISA, using a polyclonal antibody to Hsp60 to sensitise polystyrene plates and a commercially available human Hsp60 as an antigen. RESULTS: The overall prevalence of H pylori infec- tion was 78.7% (n = 63) in patients and 76.2% (n = 122) in controls (P = 0.07). Patients infected by CagA- positive (CagA+) H pylori strains were 71.4% (n = 45) vs 52.4% of infected controls (P = 0.030, OR = 2.27). Sys-temic levels of IgG to Hsp60 were increased in H pylori- negative patients compared with uninfected controls (P < 0.001) and CagA-positive infected patients compared with CagA-positive infected controls (P = 0.007). CONCLUSION: CagA positive H pylori infection may concur to the development of CHD; high levels of anti- Hsp60 antibodies may constitute a marker and/or a con- comitant pathogenic factor of the disease.

C-reactive Protein Level,Apolipoprotein B-to-apolipoprotein A-1 Ratio,and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China

Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.

Altered serum level of cartilage oligomeric matrix protein and its association with coronary calcification in patients with coronary heart disease

Background Cartilage oligomeric matrix protein （COMP） is mainly found in the skeletal system and vascular smooth muscle cells. Recent researches showed that it had a protective function on blood vessels and could also inhibit vascular calcification. We investigated the serum COMPs in coronary heart disease （CHD） patients, and the relationship between serum COMP and the calcification of coronary artery. Methods A total of 233 consecutive chest pain patients who first underwent coronary angiography followed by multi-slice computed to- mography （MSCT） within six months were recruited and divided into two groups according to the coronary angiography luminal diameter narrowing percentages： CHD group （diameter narrowing 〉 50%, n = 194） and control group （diameter narrowing 〈 50%, n = 39）. The Gen- sini score, Syntax score and coronary artery calcium score （CACs） were calculated. The serum COMP level was determined using ELISA. Results The levels of COMP were significantly higher in the CHD group than in the control group 155.7 （124.5-194.5） ng/mL vs. 128.4 （113.0-159.9） ng/mL, P = 0.019. There were no correlation between COMP, Gensini score, Syntax score, severity of coronary stenosis and the number of coronary artery with stenosis 〉 50%. The serum COMP was correlated with age （r = 0.294, P 〈 0.001）, fasting glucose （r = 0.163, P = 0.015）, HbAlc （r = 0.194, P = 0.015） and CACs （r = 0.137, P = 0.037）. Stepwise linear regression analysis showed that COMP level and age were independent predictors of CACs in the CHD patients （fl = 0.402, t = 2.612, P = 0.015; fl = 0.472, t = 3.077, P = 0.005）. Performance of COMP for predicting CHD was shown as area under curve （AUC）： 0.632, 95% CI： 0.549-0.715 and upper tertile CACs was AUC： 0.602, 95% CI： 0.5264）.678 in receiver operating characteristic （ROC） curve analysis. Conclusion Calcification of coronary artery was an independent predictor of serum COMPs.

High sensitivity C-reactive protein and cardfiac resynchronization therapy in patients with advanced heart failure

Background The data on the prognostic values of high sensitivity C-reactive protein （hsCRP） levels in patients with advanced symp-tomatic heart failure （HF） receiving cardiac resynchronization therapy （CRT） are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome. Methods A total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF. Results During the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP （〉3 mg/L） prior to CRT was associated with a significant 2.39-fold increase （P=0.006） in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels （–0.5 ± 4.1 mg/L reduction） compared with non-responders （1.7 ± 6.1 mg/L increase, P=0.018）. Com-pared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations （Log-rank P〈0.001）. The echocardio-graphic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high. Conclusions Our findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.

Myeloperoxidase and High-Sensitivity C-Reactive Protein for Predicting Major Adverse Cardiovascular Events in Patients with Coronary Heart Disease

Background: Research has shown that high-sensitivity C-reactive protein (hs-CRP) is a major inflammatory marker for prediction of acute coronary syndrome (ACS). Myeloperoxidase (MPO) also plays an important role in atherosclerosis initiation and development. In present study, the major adverse cardiovascular events (MACEs) of patients with coronary heart disease (CHD) were investigated. Methods: MPO, hs-CRP and ACS-related risk factors from 201 ACS (78 AMI and 123 UAP) and 210 non-ACS (84 SAP and 126 non-CHD) patients confirmed by coronary angiography were detected, and the data were analyzed with receiver operating characteristic (ROC) curve and Spearman’s correlation coefficients. MACEs of 285 CHD patients were investigated during the 4-year period follow-up from March 2010 to May 2014. Results: The areas under ROC curve for diagnosing ACS were 0.888 (95% CI 0.843 - 0.933) for MPO, and 0.862 (95% CI 0.815-0.910) for hs-CRP, respectively. There were significantly correlations between MPO and hs-CRP in both ACS and non-ACS groups. Regarding to ACS patients, both MPO and hs-CRP were positively correlated with BMI, TC, TG, LDL-C and Hcy. Prospective study demonstrated that the incidences of MACEs associated significantly with elevated MPO baseline level (yes vs no, OR 7.383, 95% CI 4.095 - 13.309) and high hs-CRP baseline level (yes vs no, OR 4.186, 95% CI 2.469 - 7.097) in CHD patients. Conclusions: The present study provides the epidemiological evidence that elevated baseline MPO and hs-CRP levels are both valuable predictors of MACEs in CHD patients. MPO and hs-CRP would prompt the progression of atherosclerosis and development from SAP to ACS.

Depression is associated with increased C-reactive protein levels in patients with heart failure and hyperuricemia

Psychological depression is considered a major determinant of health status in patients with heart failure （HF）. The incidence of depression in HF is four to five times higher than that in the general population.

Dietary Magnesium Intake Related to C-Reactive Protein in Newly Diagnosed Coronary Heart Disease Patients at Middle Zone, Gaza Strip. A Hospital Based Study

Coronary Heart Disease (CHD) is a highly prevalent disease all over the world. Magnesium (Mg) plays a role in CHD but it is still unclear. C-Reactive Protein (CRP) is an inflammatory marker which may rise in CHD. Aim of study: To assess the impact of dietary Mg intake and its level in relation to CRP among newly diagnosed CHD at middle zone of Gaza Strip. Methodology: Patients (n = 140) with confirmed CHD, 50 ± 10 years, presented in the cardiac care unit at Aqsa Martyr’s Hospital between 1 April 2012 and 30 December 2012, were enrolled in this cross-sectional study after taking consent. ECG, clinical status, and cardiac markers were used to confirm diagnosis by cardiologist. Food frequency questionnaire was used to assess Mg intake and calcium intake in addition to measurement of its level in serum. CRP latex slide was used for measurement of CRP. Results: Mg intake and serum Mg were?inversely associated with risk?of CHD. Mean of serum Mg among cases (1.80) was lower than controls (2.41) (P = 0.001). Percent of positive CRP was higher in cases (32.9%) than controls (12.9%) (P = 0.005). Mean of serum Mg was (1.96 ± 0.47) for positive CRP which was lower than the mean of serum Mg (2.15 ± 0.44) for negative CRP. Conclusion: Newly diagnosed patients with CHD have a positive CRP, low serum and low?Mg intake, and low serum Mg was associated with elevated CRP.

Nursing care of a patient with programmed cell death protein-1 immunotherapy-related myocarditis combined with coronary heart disease

This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart disease(CHD)after receiving said treatment.In this case,immune myocarditis with CHD occurred shortly after implementing the PD-1 immunotherapy,yet the patient presented no clinical symptoms.Frequent nursing attention and close observation are so required for monitoring the patient’s status and updating the physicians for a swift control of the myocarditis.For this case,nursing care procedures vital for the successful recovery of the patient included condition observation,position management,pre-and postcoronary angiography care,infection prevention,hemorrhage prevention,venous access port maintenance,pain care,trachea care,psychological care,diet care,environment management,and health education.After receiving effective,successful treatment and care,the patient was discharged after 13 days of treatment with generally satisfying overall conditions.

HEART FAILURE MYOCYTE CONTRACTILE MECHANICS AND ITS CONTRACTILE PROTEIN GENE EXPRESSION

It is not certain whether the myocyte contractile function in the heartfailure is normal according to recent some studies,therefore the contractile functionof the myocytes with the heart failure should be studied. The myocyte heart failuremodel was set up by the method of stretching the cultured myocytes,and the myocytes with and without the heart failure were measured the contractile mechanicscharacteristic,the parameters being the maximal contractive velocity of the myocyte(Vmax), the maximal shortening length of myocyte contraction (ΔLmax) and themaximal decrease of the myocyte size during contraction (ΔSmax), by the videoedgedetector system. And then the protein genes (including α-MHC and β-MHC)expression of these myocytes were quantitatively measured by the dot blotting. Thecorrelative and regressive analysis were used to analyze the relationship between themyocyte contractile mechanics characteristic and the contractile protein genes expression level. The results showed that the contractile mechanics parameters,Vmax=41．5±6．0(μm/sec), △Lmax= 10．6±1．9 (% ) and △Smax= 14．3± 2．3 (% ), in themyocytes with the heart failure are statistically significant lower than the normalmyocytes (P<0．01), whose parameters are Vmax=67．9±6．7 (μm/sec), △Lmax=17．7±1．6 (% ) and △Smax=21．5±2．4 (%). The myocyte contractile protein gene (αMHC) expression level in the heart failure myocytes is statistically significant lowerthan that in the normal myocytes,but β-MHC gene expression level is statisticallysignificant higher than the normal myocytes. The α-MllC gene expression level is apositive correlation coefficient with the myocyte contractile mechanics parametersseparately,covering Vmax,△Lmax and △max; but the β- MHC gene expression levelis a negative correlation coefficietn with the myocyte contractile mechanics parameters separately.

Expression and Characterization of Human Heart Type Fatty Acid Binding Protein in Pichia Pastoris

H-FABP is regarded as a tissue-specific protein existing only in myocardial cells. It is released from the cardiac tissue and gets into the plasma when a heart attack occurs; the myocardial infarction is a good case in point. As a resuit, the detection of H-FABP will be an early and important biomarker for the disease concerned. The objective of the study is to prepare the recombinant H-FABP by aeukaryotic expression system, pichia, to produce the protein mimicking natural H-FABP, as an immunogen for the production of the specific antibody. A gene fragment encoding H-FABP was cloned in the expressing vector pPICZα, after sequencing. The recombinant plasmid was transformed into the competent cells of the X-33 strain by means of electroporation. The expression of the target peptide induced by methanol was screened by means of Western hlotting, with the available MAb（Clone 6B6）. Highly expressive engineer strains were obtained. The production of recombinant H-FABP under induction was about 0.7 g/L, with an Mr of 14.5 kDa and recognized by a commercially available MAb （Clone 6B6）. The recombinant vector was successfully constructed. Following this, H-FABP was expressed in X-33, and it would become the source of the preparation of specific antibodies, to develop diagnostic kits.

Sequencing of Intron 3 of Porcine Heart Fatty Acid-Binding Protein Gene

[ Objective] The aim of this paper is to provide the basic data for marker-assisted selection of pig breeding using porcine heart fatty acid- binding protein （H-FABP） gene. [Method] According to the related sequences of porcine H-FABP gene released in GenBank, specific primers were designed to amplify the intron 3 of porcine H-FABP gene. [ Result] The intron 3 of porcine H-FABP gene was amplified successfully. Its whole sequence was 1 350 bp in length and had been submitted to GenBank （Accession no. ： DQ 002993）. [Condusion] The study lays a theoretical foundation for determination of the major genes affecting intramuscular fat deposition.

Role of thrombus precursor protein in assessment of anticoagulation in patients with atrial fibrillation after mechanical heart valve replacement

Objective: To explore the role of thrombus precursor protein (TpP) in assessment of anticoagulation and predict the risk of thromboembolism in the patients with atrial fibrillation (AF) after mechanical heart valve replacement. Methods: TpP plasma concentration and international normalization ratio (INR) were measured in 45 patients with atrial fibrillation and 45 patients with sinus rhythm both after mechanical heart valve replacement. Twenty patients with non valvular heart diseases were selected as the control. Furthermore, the patients with AF were divided into groups based on different TpP plasma concentration and TpP plasma concentration and INR were analyzed. Results: After mechanical heart valve replacement, those with AF had higher TpP plasma concentration than those with sinus rhythm. It was found that discordancy existed between INR and TpP plasma concentration in the patients with AF. There were 28 AF patients with TpP plasma concentration lower than 6 μg/ml and without bleeding, who might be at the optimal anticoagulant state. The 95% confidence of the mean INR value was 1.90-2.30 in these patients and TpP plasma concentration was between 2.84-5.74 μg/ml. Conclusion: Patients with AF might face higher risk of thromboembolism after mechanical valve replacement; INR between 1.90-2.30 and TpP plasma concentration between 2.84-6 μg/ml might be the optimal anticoagulant range for patients with AF after mechanical valve replacement.

Effects of Huang Qi Wu Wu Decoction on Plasma Proteins in 70 Cases of Chronic Pulmonary Heart Disease

Simple immune agar diffusion test was used to assay the contents of 12 plasma proteins in 70 cases of chronic pulmonary heart disease treated by Huang Qi Wu Wu Decoction (黄芪五物汤), with the other 70 cases who were not given Huang Qi Wu Wu Decoction as the control group. The total clinical effective rate in the treatment group was 90.0%, while that in the control group was 75.7%, with a statistically significant difference between the two groups (P<0.05). In the treatment group, the levels of prealbumin, transferrin and fibronectin elevated obviously after treatment, and the contents of C-reactive protein, ceruloplasmin, haptoglobin, a 1-antitrypsin and a 1-acid glycoprotein decreased markedly (P<0.01). In the control group, only the levels of ceruloplasmin and C-reactive protein decreased significantly (P<0.05). It is shown that Huang Qi Wu Wu Decoction may enhance the therapeutic effects for pulmonary heart disease, regulate the metabolism of plasma proteins, and improve the life quality of the patients.

Correlation between serum C1q tumor necrosis factor-related protein 4 and high-sensitivity C-reactive protein levels and coronary heart disease

Objective:To investigate the relationship between serum levels of C1q tumor necrosis factorrelated protein 4(CTRP4)and hypersensitive C reactive protein(hs-CRP)and coronary heart disease(CHD)and its clinical value.Methods:128 patients underwent coronary angiography in our hospital,63 males,65 women,Based on blood sugar levels and coronary angiography,Divided into pure coronary heart disease(CHD)group 62 cases,Coronary heart disease with diabetes(DM+CHD)group 66 cases,A total of 126 patients were selected as control group,65 men,61 women,CTRP4 and hs-CRP levels in serum,Using Pearson correlation analysis to assess the correlation between Gennisi score and CTRP4、hs-CRP,Analysis of three groups of biochemical indicators,CTRP4、hs-CRP level changes and clinical significance.Results:The CTRP4、hs-CRP level of DM+CHD group was significantly higher than that of control group and CHD group(P DM+CHD 0.05).The CTRP4、hs-CRP level of the three-vessel coronary artery lesion group in the experimental group was higher than that in the two-vessel lesion group(P﹤0.05),Double branch lesion group was higher than single branch lesion group(P﹤0.05);Correlation analysis shows,There was a significant positive correlation between the CTRP4、hs-CRP level of CHD group and DM+CHD group and the Gennisi score(P DM+CHD 0.05).ROC curves show,CTRP4 and hs-CRP levels had predictive value(CHD group,AUC=0.940,0.934,DM+CHD group,AUC=0.980,0.964),Two associations(CHD:AUC=0.961,P﹤0.001,DM+CHD group:AUCDM+CHD 0.982,P﹤0.001)the predictive value is high.Conclusion:Serum CTRP4 and hs-CRP are positively related to the severity of coronary heart disease,and the sensitivity and specificity of predicting coronary heart disease are high,which is helpful for the identification and early prevention of coronary heart disease,and has certain clinical reference value.

Amelioration of mitochondrial dysfunction in heart failure through S-sulfhydration of Ca^2＋/calmodulin-dependent protein kinase Ⅱ

OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) using wild type and CSE knockout mouse models.METHODS Continuous subcutaneous injection isoprenaline(7.5 mg·kg^(-1) per day),once a day for 4 weeks to induce heart failure in male C57BL/6(6-8 weeks old) mice and CSE-/-mice.150 μmol·L^(-1) H_2O_2 was used to induce oxidative stress in H9c2 cells.Echocardiograph was used to detect cardiac parameters.H&E stain and Masson stain was to observation histopathological changes.Western blot was used to detect protein expression and activity.The si RNA was used to silence protein expression.HPLC was used to detect H_2S level.Biotin assay was used to detect the level of S-sulfhydration protein.RESULTS Treatment with S-propyl-L-cysteine(SPRC) or sodium hydrosulfide(Na HS),modulators of blood H_2S levels,attenuated the development of heart failure in animals,reduced lipid peroxidation,and preserved mitochondrial function.The inhibition Ca MKⅡ phosphorylation by SPRC and Na HS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds.Interestingly,Ca MKⅡ activity was found to be elevated in CSE-/-mice as compared to wild type animals and the phosphorylation status of Ca MK Ⅱ appeared to relate to the severity of heart failure.Importantly,in wild type mice SPRC was found to promote S-sulfhydration of Ca MKⅡ leading to reduced activity of this protein however,in CSE-/-mice S-sulfhydration was abolished following SPRC treatment.CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of Ca MKⅡ is presented.SPRC mediated S-sulfhydration of Ca MKⅡ was found to inhibit Ca MKⅡ activity and to preserve cardiovascular homeostasis.

Gene polymorphisms associated with sudden decreases in heart rate during extensive peritoneal lavage with distilled water after gastrectomy

BACKGROUND Our previous study found that the telomerase-associated protein 1(TEP1,rs938886 and rs1713449)and homo sapiens RecQ like helicase 5(RECQL5,rs820196)single nucleotide polymorphisms(SNPs)were associated with changes in heart rate(HR)≥30%during peritoneal lavage with distilled water after gastrectomy.This study established a single tube method for detecting these three SNPs using two-dimensional(2D)polymerase chain reaction(PCR),and investigated whether SNP-SNP and SNP-environment interactions increase the risk of high HR variability(HRV).AIM To investigate whether genotypes,genetic patterns,SNP-SNP and SNP-environment interactions were associated with HRV.METHODS 2D PCR was used to establish a single-tube method to detect TEP1 rs938886 and rs1713449 and RECQL5 rs820196,and the results were compared with those of sanger sequencing.After adjusting for confounders such as age,sex,smoking,hypertension,and thyroid dysfunction,a nonconditional logistic regression model was used to assess the associations between the genotypes and the genetic patterns(codominant,dominant,overdominant,recessive,and additive)of the three SNPs and a risk≥15%or≥30%of a sudden drop in HR during postoperative peritoneal lavage in patients with gastric cancer.Gene-gene and geneenvironment interactions were analyzed using generalized multifactor dimensionality reduction.RESULTS The coincidence rate between the 2D PCR and sequencing was 100%.When the HRV cutoff value was 15%,the patients with the RECQL5(rs820196)TC genotype had a higher risk of high HRV than those who had the TT genotype(odds ratio=1.97;95%CI:1.05-3.70;P=0.045).Under the codominant and overdominant models,the TC genotype of RECQL5(rs820196)was associated with a higher risk of HR decrease relative to the TT and TT+CC genotypes(P=0.031 and 0.016,respectively).When the HRV cutoff value was 30%,patients carrying the GC-TC genotypes of rs938886 and rs820196 showed a higher HRV risk when compared with the GG–TT genotype carriers(P=0.01).In the three-factor model of rs938886,rs820196,and rs1713449,patients carrying the GC-TC-CT genotype had a higher risk of HRV compared with the wild-type GG-TT-CC carriers(P=0.01).For rs820196,nonsmokers with the TC genotype had a higher HRV risk compared with nonsmokers carrying the TT genotype(P=0.04).When the HRV cutoff value was 15%,patients carrying the TT-TT and the TC-CT genotypes of rs820196 and rs1713449 showed a higher HRV risk when compared with TT-CC genotype carriers(P=0.04 and 0.01,respectively).Patients carrying the GC-CT-TC genotypes of rs938886,rs1713449,and rs820196 showed a higher HRV risk compared with GG-CC-TT genotype carriers(P=0.02).When the HRV cutoff value was 15%,the best-fitting models for the interactions between the SNPs and the environment were the rs820196-smoking(P=0.022)and rs820196-hypertension(P=0.043)models.Consistent with the results of the previous grouping,for rs820196,the TC genotype nonsmokers had a higher HRV risk compared with nonsmokers carrying the TT genotype(P=0.01).CONCLUSION The polymorphism of the RECQL5 and TEP1 genes were associated with HRV during peritoneal lavage with distilled water after gastrectomy.

Clinical perspective on C-reactive protein in prognostication of major adverse cardiac events in the elderly with established coronary heart disease

The systemic response to tissue injury, regardless of cause is characterized by a cytokine-mediated alteration in the hepatic synthesis of a number of different plasma proteins,known collectively as 'acute phase reactants'. These proteins include C-reactive protein, serum amyloid A protein, alphal glycoprotein, ceruloplasmin, alpha macroglobulins, complement components (C1-C4, factor B, C9, C11), alpha1antitrypsin, alpha1 antichymotrypsin, fibrinogen, prothrombin,factor Ⅷ, plasminogen, haptoglobin, ferritin, immunoglobulins and lipoproteins. The initiation of the acute phase response is linked to the production of hormone-like polypeptide mediators now called cytokines, namedly, interleukin 1(IL-1),tumor necrosis factor, interferon gamma, interleukin 6 (IL-6),leukemia inhibitory factor, ciliary neurotropic factor, oncostatin M, and interleukin 11 (IL- 11).……