Serum uric acid and outcome in hospitalized elderly patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes.

INTRODUCTION: Elevated serum uric acid (SUA) levels have been associated with poor outcome in patients with heart failure (HF). Uric acid is associated with inflammation and microvascular dysfunction, which may differentially affect left ventricular ejection fraction (EF) phenotypes. We aimed to identify the role of SUA across EF phenotypes in hospitalized elderly patients with chronic HF. METHODS: We analyzed 1355 elderly patients who were diagnosed with chronic HF. All patients had SUA levels measured within the first 24 h following admission. Patients with left ventricle EF were categorized as having HF with reduced EF (HFrEF, EF < 40%), HF with mid-range EF (HFmrEF, 40%≦LVEF ≦ 49%) or HF with preserved EF (HFpEF, LVEF ≥ 50%). Endpoints were cardiovascular death, HF rehospitalization, and their composite. The median follow-up period was 18 months. RESULTS: Compared with the lowest SUA quartile, the highest SUA quartile was significantly associated with the endpoints (adjusted HR: 2.404, 95% CI: 1.178-4.906, P = 0.016; HR: 1.418, 95% CI: 1.021-1.971, P = 0.037; HR: 1.439, 95% CI: 1.049-1.972, P = 0.024, respectively). After model adjustment, a significant association of SUA with cardiovascular death and the composite endpoint persisted among HFrEF and HFmrEF patients in the highest SUA quartile (P < 0.05 for all). CONCLUSIONS: In hospitalized elderly patients with chronic HF, SUA is an independent predictor of adverse outcomes, which can be seen in HFrEF and HFmrEF patients.

Genome-wide analysis of tunicamycin-induced endoplasmic reticulum stress response and the protective effect of endoplasmic reticulum inhibitors in neonatal rat cardiomyocytes.

Tunicamycin (TM) is an inducer of endoplasmic reticulum (ER) stress. However, which genes related to ER stress was induced in cardiomyocytes on a genome-wide scale remains poorly understood. Salubrinal and its derivatives are ER stress inhibitors. However, the cellular protection mechanisms remain unresolved. Neonatal rat cardiomyocytes were cultured from ventricles of one-day-old Wistar rats. Cells were exposed to salubrinal, its derivatives (PP1-12, PP1-24) or vehicle followed by TM treatment at different times. Total RNA was isolated from cells for RNA-sequencing analysis. The expressions of 189, 182, 556, 860, and 1314 genes were changed in cells exposed to TM for 1, 3, 6, 12, and 24 h. Five well-known UPR genes (Hspa5, Hsp90b1, Calr, Ddit3, and Atf4) were significantly increased in a time-dependent manner. Six not well-known genes (Hyou1, Herpud1, Manf, Creld2, Sdf2l1, and Slc3a2) were highlighted to be involved in ER stress. Compared with TM-only treated cells, the expressions of 36 genes upregulated by TM and 74 genes downregulated by TM were reversed by salubrinal. In comparison, 121 genes upregulated by TM and 92 genes downregulated by TM were reversed by PP1-12. Most genes altered by salubrinal are in the category of transcription (1 h) and cell cycle (24 h). Most genes altered by PP1-12 are in the category of response to ER stress (3 h) and cell cycle (24 h). Our findings help elucidate the mechanism for TM treatment and may be useful for future drug screens involved in ER stress.

Effects of PP1-12, a novel protein phosphatase-1 inhibitor, on ventricular function and remodeling after myocardial infarction in rats.

: PP1-12, a new protein phosphatase-1 inhibitor, is designed and synthesized to modulate the endoplasmic reticulum (ER) stress apoptotic pathway, which is involved in various cardiovascular diseases. In this study, we examined the effect of PP1-12 on ventricular remodeling and heart function after myocardial infarction. Rats that survived within 24 hours after coronary ligation were randomly divided into 6 groups and treated with normal saline, vehicle, PP1-12 at 1, 3, and 10 mg·kg·d and perindopril at 2 mg·kg·d for 4 weeks, respectively. At the end of the follow-up point, we evaluated echocardiographic and hemodynamic parameters, myocardial pathomorphology, apoptosis, and interstitial fibrosis, as well as the expression levels of important proteins involved in ER stress and apoptosis. Left ventricular geometry and function were ameliorated by PP1-12. PP1-12 inhibited interstitial fibrosis and reduced apoptosis of cardiomyocytes in a dose-dependent manner. PP1-12 decreased GRP78 and caspase-12 expression and increased p-eIF2α and Bcl-2/Bax expression. These results suggest that PP1-12 efficiently inhibits left ventricular remodeling and improves heart function. The mechanism involved may be associated with the ability of PP1-12 to depress myocardial apoptosis induced by ER stress.

Circulating circRNA expression profile and its potential role in late recurrence of paroxysmal atrial fibrillation post catheter ablation.

BACKGROUND: Catheter-based pulmonary vein isolation (PVI) is an effective and well-established intervention for symptomatic paroxysmal atrial fibrillation (PAF). Nevertheless, late recurrences of atrial fibrillation (LRAF) occurring during 3 to 12 months are common, and the underlying mechanisms remain elusive. Circular RNAs (circRNAs) in atrial tissue have been linked to the pathophysiological mechanisms and progression of PAF in a few studies. However, their expression patterns in peripheral blood and regulatory function in LRAF are not clear. METHODS: In the present study, the expression profile of circulating circRNAs in three paired nonvalvular PAF patients with or without LRAF was investigated by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA/miRNA regulatory network, were performed to predict the functions and potential regulatory roles of differentially expressed (DE) circRNAs. RESULTS: A total of 12,834 circRNAs, comprising 5,491 down-regulated and 7,343 up-regulated circRNAs, were found to be DE in blood smaples from the two groups in peripheral blood between LRAF and non-recurrence control individuals. The most enriched GO categories in terms of molecular function, biological process, and cellular component features were catalytic activity, cellular metabolic process, and intracellular part, respectively. The KEGG enrichment study revealed that the most important metabolic process controlled by DE circRNAs is endocytosis. In the circRNA/microRNAs interaction network, four up-regulated circRNAs (hsa_circ_0002665, hsa_circ_0001953, hsa_circ_0003831, and hsa_circ_0040533) and one down-regulated circRNA (hsa_circ_0041103) were predicted to play potential regulatory roles in the pathogenesis of LRAF. CONCLUSIONS: This investigation discovered the expression pattern of circulating circRNAs that is indicative of PAF late recurrence, which may serve as risk markers or therapeutic targets for LRAF after PVI.

GhSINA1, a SEVEN in ABSENTIA ubiquitin ligase, negatively regulates fiber development in Upland cotton.

Protein ubiquitination is essential for plant growth and responses to the environment. The SEVEN IN ABSENTIA (SINA) ubiquitin ligases have been extensively studied in plants, but information on their roles in fiber development is limited. Here, we identified GhSINA1 in Upland cotton (Gossypium hirsutum), which has a conserved RING finger domain and SINA domain. Quantitative real-time PCR (qRT-PCR) analysis showed that GhSINA1 was preferentially expressed during fiber initiation and elongation, especially during initiation in the fuzzless-lintless cotton mutant. Subcellular localization experiments indicated that GhSINA1 localized to the nucleus. In vitro ubiquitination analysis revealed that GhSINA1 has E3 ubiquitin ligase activity. Ectopic overexpression of GhSINA1 in Arabidopsis thaliana reduced the number and length of root hairs and trichomes. Yeast two-hybrid (Y2H), firefly luciferase complementation imaging (LCI), and bimolecular fluorescence complementation (BiFC) assays demonstrated that the GhSINA1 proteins could interact with each other to form homodimers and heterodimers. Overall, these results suggest that GhSINA1 may act as a negative regulator in cotton fiber development through homodimerization and heterodimerization.

Unraveling genomic regions and candidate genes for multiple disease resistance in upland cotton using meta-QTL analysis.

Verticillium wilt (VW), Fusarium wilt (FW) and Root-knot nematode (RKN) are the main diseases affecting cotton production. However, many reported quantitative trait loci (QTLs) for cotton resistance have not been used for agricultural practices because of inconsistencies in the cotton genetic background. The integration of existing cotton genetic resources can facilitate the discovery of important genomic regions and candidate genes involved in disease resistance. Here, an improved and comprehensive meta-QTL analysis was conducted on 487 disease resistant QTLs from 31 studies in the last two decades. A consensus linkage map with genetic overall length of 3006.59 cM containing 8650 markers was constructed. A total of 28 Meta-QTLs (MQTLs) were discovered, among which nine MQTLs were identified as related to resistance to multiple diseases. Candidate genes were predicted based on public transcriptome data and enriched in pathways related to disease resistance. This study used a method based on the integration of Meta-QTL, known genes and transcriptomics to reveal major genomic regions and putative candidate genes for resistance to multiple diseases, providing a new basis for marker-assisted selection of high disease resistance in cotton breeding.

[Assessment of the right ventricular function in healthy volunteers with one beat full-volume real-time three-dimensional echocardiography].

OBJECTIVE: To determine the normal value of right ventricle using one beat full-volume real-time three-dimensional echocardiography (RT-3DE) and assess the feasibility of this technique. METHODS: One beat full volume images were acquired at the apical 4 chamber view in 129 healthy volunteers. The right and left ventricular volumes were examined with the eSie LVA and RVA. The subjects were divided into 2 gender groups (male and female) and 3 age groups (20 - 39 years old, 40 - 59 years old, 60 years old and above). RESULTS: Adequate data were obtained in 129 subjects. The RV-EDV was (92.4 ± 21.3) ml, RV-ESV (34.6 ± 9.2) ml, RV-SV (57.8 ± 13.9) ml, RV-EF (62.5 ± 5.0) ml. EDV, ESV, and EF were significant different while SV was similar between RV and LV (all P < 0.05). RV-EDV (r = 0.517, P = 0.001), RV-ESV (r = 0.588, P = 0.001) and RV-SV(r = 0.409, P = 0.001) were correlated well with BSA. RV-EDV, RV-ESV and RV-SV were significantly higher in males than in females (all P < 0.001). RV-EDV, RV-SV and RV-EF decreased with aging (P < 0.05). CONCLUSIONS: Right ventricle function can be measured noninvasively by RT-3DE with high feasibility. This novel method contributes to the detailed study of right heart function in various cardiovascular diseases.

Incidence, risk factors and prognosis of acute kidney injury in patients treated with immune checkpoint inhibitors: a retrospective study.

Immune checkpoint inhibitors (ICIs) change the prognosis of many cancer patients. With the increasing use of ICIs, immune-related adverse events are occurring, including acute kidney injury (AKI). This study aimed to assess the incidence of AKI during ICI treatment and its risk factors and impact on mortality. Patients treated with ICIs at the First Medical Center of the Chinese PLA General Hospital from January 1, 2014, to December 30, 2019, were consecutively enrolled, and risk factors affecting AKI development in patients treated with ICIs were analyzed using univariate and multivariate logistic regression. Medical record surveys and telephone inquiry were used for follow-up, and Kaplan-Meier survival analysis and Cox regression were used to analyze independent risk factors for death. Among 1615 patients, 114 (7.1%) had AKI. Multivariate logistic regression analysis showed that anemia, Alb < 30 g/L, antibiotic use, diuretic use, NSAID use and proton pump inhibitor use were independent risk factors for AKI development in patients treated with ICIs. Stage 2 or 3 AKI was an independent risk factor for nonrecovery of renal function after AKI onset. Multivariate Cox regression analysis showed that anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs, while high baseline BMI, other tumor types, ACEI/ARB use, and chemotherapy use were protective factors for patient death. AKI occurs in 7.1% of patients treated with ICIs. Anemia, Alb < 30 g/L, and combined medication use are independent risk factors for AKI in patients treated with ICIs. Anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs.

The impact of extra cardiac comorbidities on pressure volume relations in heart failure and preserved ejection fraction.

BACKGROUND: Extracardiac comorbidities are common in patients with heart failure and a preserved ejection fraction (HFPEF). We sought to evaluate the relationship between comorbidities and ventricular structure and function in patients with HFPEF through evaluation of pressure-volume analysis. METHODS AND RESULTS: Two hundred twenty Chinese patients with a preserved ejection fraction who were either healthy (n = 75), hypertensive without heart failure (HTN; n = 89), or hypertensive with HFPEF (HFPEF; n = 56) were studied. Using echocardiographic measures, estimated end-systolic and end-diastolic pressure-volume relationships, and the area between them as a function of EDP, the isovolumic pressure-volume areas (PVA(iso)), were calculated. Ventricular capacitance, as measured by V(30), was larger in patients with HFPEF compared with normal control subjects and tended to be larger compared with hypertensive control subjects. The presence of diabetes and renal insufficiency was independently associated with greater ventricular capacitance in patients with HFPEF. The PVA(iso) was increased in patients with HFPEF compared with HTN and normal control subjects, and in particular, it was increased in HFPEF patients with multiple comorbidities. CONCLUSIONS: The presence of comorbid conditions is associated with altered pressure-volume relations and enhanced pump function in subjects with HFPEF, supporting an important role for extracardiac comorbidities in the pathophysiology of patients with this condition.

[Research of endoplasmic reticulum stress and cardiovascular diseases].

Endoplasmic reticulum stress is a newly discovered pathway of apoptosis, following the death receptor signaling and mitochondrial pathways. Moderate stress triggers the unfolded protein response (UPR) to rsstore the cell function. However, if the stress is severe and/or prolonged, the ER also initiates apoptotic signaling that includes CHOP, ASK1/JNK and caspases pathways. Recent studies have found that endoplasmic reticulum stress plays an important role in the development of various cardiovascular diseases. Also, extensive research has shown that it can bring about protective effects on myocardial cells through the intervention of the relevant pathways, which may provide us with new therapeutic targets for heart diseases.

Effects of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors on COVID-19.

BACKGROUND: The World Health Organization reported that 28637952 people worldwide had been infected with severe acute respiratory syndrome coronavirus 2, the causative agent of coronavirus disease 2019 (COVID-19), by September 13. AIM: The aim was to investigate whether long-term use of renin-angiotensin-aldosterone system (RAAS) inhibitors for the treatment of hypertension aggravates the performance of COVID-19 patients with hypertension. METHODS: This was a retrospective analysis of lung computed tomography (CT) data and laboratory values of COVID-19 patients with hypertension who were admitted to Huoshenshan Hospital, Wuhan, Hubei Province, between February 18 and March 31, 2020. Patients were divided into two groups. Group A included 19 people who were long-term users of RAAS inhibitors for hypertension; and group B included 28 people who were randomly selected from the database and matched with group A by age, sex, basic diseases, and long-term use of other antihypertensive drugs. All patients underwent a series of CT and laboratory tests. We compared the most severe CT images of the two groups and the laboratory examination results within 2 d of the corresponding CT images. RESULTS: The time until the most severe CT images from the onset of COVID-19 was 30.37 ± 14.25 d group A and 26.50 ± 11.97 d in group B. The difference between the two groups was not significant (t = 1.01, P = 0.32). There were no significant differences in blood laboratory values, C-reactive protein, markers of cardiac injury, liver function, or kidney function between the two groups. There was no significant difference in the appearance of the CT images between the two groups. The semiquantitative scores of each involved lobe were 11.84 ± 5.88 in group A and 10.36 ± 6.04 group B. The difference was not significantly different (t = 0.84, P = 0.41). CONCLUSION: Chest CT is an important imaging tool to monitor the characteristics of COVID-19 and the degree of lung injury. Chronic use of RAAS inhibitors is not related to the severity of COVID-19, and it does not worsen the clinical process.

Network of Interactions Between Gut Microbiome, Host Biomarkers, and Urine Metabolome in Carotid Atherosclerosis.

Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.

Genetic structure, gene flow pattern, and association analysis of superior germplasm resources in domesticated upland cotton (Gossypium hirsutum L.).

Gene flow patterns and the genetic structure of domesticated crops like cotton are not well understood. Furthermore, marker-assisted breeding of cotton has lagged far behind that of other major crops because the loci associated with cotton traits such as fiber yield and quality have scarcely been identified. In this study, we used 19 microsatellites to first determine the population genetic structure and patterns of gene flow of superior germplasm resources in upland cotton. We then used association analysis to identify which markers were associated with 15 agronomic traits (including ten yield and five fiber quality traits). The results showed that the upland cotton accessions have low levels of genetic diversity (polymorphism information content = 0.427), although extensive gene flow occurred among different ecological and geographic regions. Bayesian clustering analysis indicated that the cotton resources used in this study did not belong to obvious geographic populations, which may be the consequence of a single source of domestication followed by frequent genetic introgression mediated by human transference. A total of 82 maker-trait associations were examined in association analysis and the related ratios for phenotypic variations ranged from 3.04% to 47.14%. Interestingly, nine SSR markers were detected in more than one environmental condition. In addition, 14 SSR markers were co-associated with two or more different traits. It was noteworthy that NAU4860 and NAU5077 markers detected at least in two environments were simultaneously associated with three fiber quality traits (uniformity index, specific breaking strength and micronaire value). In conclusion, these findings provide new insights into the population structure and genetic exchange pattern of cultivated cotton accessions. The quantitative trait loci of domesticated cotton identified will also be very useful for improvement of yield and fiber quality of cotton in molecular breeding programs.

PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure.

The type 1 ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR) is the major calcium (Ca2+) release channel required for skeletal muscle excitation-contraction (EC) coupling. RyR1 function is modulated by proteins that bind to its large cytoplasmic scaffold domain, including the FK506 binding protein (FKBP12) and PKA. PKA is activated during sympathetic nervous system (SNS) stimulation. We show that PKA phosphorylation of RyR1 at Ser2843 activates the channel by releasing FKBP12. When FKB12 is bound to RyR1, it inhibits the channel by stabilizing its closed state. RyR1 in skeletal muscle from animals with heart failure (HF), a chronic hyperadrenergic state, were PKA hyperphosphorylated, depleted of FKBP12, and exhibited increased activity, suggesting that the channels are "leaky." RyR1 PKA hyperphosphorylation correlated with impaired SR Ca2+ release and early fatigue in HF skeletal muscle. These findings identify a novel mechanism that regulates RyR1 function via PKA phosphorylation in response to SNS stimulation. PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF.

Myoblast transfer in ischemic heart failure: effects on rhythm stability.

Skeletal myoblast (SM) implantation promotes recovery of myocardial function after ischemic injury. Clinical observations suggest an association of SM implantation and ventricular arrhythmias. Support for this link has been sought in animal studies, but none employing models of congestive heart failure. In a canine model of postinfarction congestive heart failure (CHF) we compared the frequency of rhythm disturbances using ambulatory electrocardiography monitoring following skeletal myoblast or saline (SAL) implantation. In 19 mongrel dogs ischemic injury and CHF were induced by intracoronary microsphere infusions. Direct intramyocardial injection of autologous skeletal myoblasts (ASM) (2.7-8.3 x 10(8) cells) or SAL controls was administered to 11 and 8 dogs, respectively. Serial echocardiography and 24-h ambulatory electrocardiography were recorded at baseline (after CHF induction) and at 4 weeks and at 8-10 weeks after injection. Comparisons between groups of left ventricular ejection fraction (LVEF) and the frequency of ventricular arrhythmias, supraventricular arrhythmias, and measures of heart rate variability (HRV) were made at each of the three time points. LVEF increased from 41 +/- 6% to 47 +/- 2% (p < 0.03) in the ASM group, and did not change (42 +/- 6% to 40 +/- 2%, p = ns) in SAL. After injection, no differences were seen in the number of dogs demonstrating ventricular tachycardia (n = 3 vs. n = 2, p = ns) or frequent PVCs (n = 3 vs. n = 3, p = ns) in the ASM versus SAL groups, respectively. Significant changes were observed in a time-domain measure of HRV, standard deviation of normal-to-normal RR interval (in ms: 4 weeks 174 +/- 95 vs. 242 +/- 19; 8 weeks 174 +/- 78 vs. 276 +/- 78, ASM vs. SAL), but not in other time domain parameters. In this canine model of ischemic CHF, ASM implantation did not result in a significant increase in ventricular arrhythmias compared to controls animals. The potential for ASM implantation to affect time-domain parameters of HRV merits further study.

Assessing inflammation in Chinese subjects with subtypes of heart failure: an observational study of the Chinese PLA Hospital Heart Failure Registry.

BACKGROUND: Inflammation is an important element of the pathophysiological process of heart failure (HF) and is correlated with subtypes of HF. The association between multiple biomarkers of inflammation and HF subtypes in Chinese subjects remains unclear. This study aimed to compare the differences in inflammation biomarkers among Chinese patients with different subtypes of HF who have been identified to date. METHODS: We included 413 consecutive patients with HF, including 262 with preserved ejection fraction (HFpEF), 55 with middle-ranged ejection fraction (HFmrEF) and 96 with reduced ejection fraction (HFrEF). Ten inflammation biomarkers were analyzed and compared according to the HF subtypes. One hundred contemporary non-HF subjects were also recruited as the control group. Moreover, the correlations between the inflammatory biomarkers and left ventricular ejection fraction of the HF subtypes were assessed. RESULTS: The mean age of the HF patients was 65.0 ± 12.0 years, 65.8% were male. Distinct subtypes of HF demonstrated different inflammation biomarker panels. IL-6, PTX-3, ANGPTL-4 and TNF-α were correlated with HFrEF; IL-1ß and PTX-3 were correlated with HFmrEF; and IL-1ß and IL-6 were correlated with HFpEF. The multivariable logistic regression showed that IL-1ß [relative ratio (RR) = 1.08, 95% CI: 1.02-1.15, P = 0.010], IL-6 (RR = 1.03, 95% CI: 1.01-1.06, P = 0.016), PTX-3 (RR = 1.31, 95% CI: 1.11-1.55, P = 0.001), and ANGPTL-4 (RR = 1.05, 95% CI: 1.02-1.07, P < 0.001) were independently associated with HF, while IL-6 (RR = 1.03, 95% CI: 1.01-1.04, P = 0.019), PTX-3 (RR = 1.23, 95% CI: 1.06-1.43, P = 0.007), and ANGPTL-4 (RR = 1.03, 95% CI: 1.01-1.06, P = 0.005) were independently associated with the HF subtype. CONCLUSIONS: Diverse inflammation biomarkers have multifaceted presentations according to the subtype of HF, which may illustrate the diverse mechanisms of inflammation in Chinese HF patients. IL-6, PTX-3, and ANGPTL-4 were independent inflammation factors associated with HFrEF and HF.

Comparative Chloroplast Genomics of Gossypium Species: Insights Into Repeat Sequence Variations and Phylogeny.

Cotton is one of the most economically important fiber crop plants worldwide. The genus Gossypium contains a single allotetraploid group (AD) and eight diploid genome groups (A-G and K). However, the evolution of repeat sequences in the chloroplast genomes and the phylogenetic relationships of Gossypium species are unclear. Thus, we determined the variations in the repeat sequences and the evolutionary relationships of 40 cotton chloroplast genomes, which represented the most diverse in the genus, including five newly sequenced diploid species, i.e., G. nandewarense (C1-n), G. armourianum (D2-1), G. lobatum (D7), G. trilobum (D8), and G. schwendimanii (D11), and an important semi-wild race of upland cotton, G. hirsutum race latifolium (AD1). The genome structure, gene order, and GC content of cotton species were similar to those of other higher plant plastid genomes. In total, 2860 long sequence repeats (>10 bp in length) were identified, where the F-genome species had the largest number of repeats (G. longicalyx F1: 108) and E-genome species had the lowest (G. stocksii E1: 53). Large-scale repeat sequences possibly enrich the genetic information and maintain genome stability in cotton species. We also identified 10 divergence hotspot regions, i.e., rpl33-rps18, psbZ-trnG (GCC), rps4-trnT (UGU), trnL (UAG)-rpl32, trnE (UUC)-trnT (GGU), atpE, ndhI, rps2, ycf1, and ndhF, which could be useful molecular genetic markers for future population genetics and phylogenetic studies. Site-specific selection analysis showed that some of the coding sites of 10 chloroplast genes (atpB, atpE, rps2, rps3, petB, petD, ccsA, cemA, ycf1, and rbcL) were under protein sequence evolution. Phylogenetic analysis based on the whole plastomes suggested that the Gossypium species grouped into six previously identified genetic clades. Interestingly, all 13 D-genome species clustered into a strong monophyletic clade. Unexpectedly, the cotton species with C, G, and K-genomes were admixed and nested in a large clade, which could have been due to their recent radiation, incomplete lineage sorting, and introgression hybridization among different cotton lineages. In conclusion, the results of this study provide new insights into the evolution of repeat sequences in chloroplast genomes and interspecific relationships in the genus Gossypium.

Repeated measurement of growth-differentiation factor-15 in Chinese Han patients with post-myocardial infarction chronic heart failure.

BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a promising prognostic biomarker in patients with chronic heart failure (CHF). Comparatively little is known about the value of repeated measurement of GDF-15 with CHF in Chinese Han population. This study sought to identify the clinical value of repeated measurement of GDF-15 in Chinese Han patients with post-myocardial infarction CHF. METHODS: In total, 232 consecutive Chinese Han patients with post-myocardial infarction CHF were enrolled prospectively from January 2014 to June 2016.The plasma concentration of GDF-15 was determined on admission and over 12 months. Patients were followed up for all-cause death and a composite outcome of major adverse cardiac events (MACE) included all-cause death, myocardial infarction and first heart failure (HF) re-hospitalization. Association with other clinical variables and adverse outcomes of repeated measurement of GDF-15 was explored. RESULTS: The median baseline GDF-15 level was 2025 ng/L. Baseline GDF-15 was moderately associated with baseline N-terminal pro-B type natriuretic peptide (NT-proBNP) (coefficient 0.561, P < 0.001). During a median follow-up of 20 months, there were 53 deaths and 100MACE. GDF-15 remained an independent predictor of all-cause death (adjusted hazard ratio 1.826 per 1 Ln U, 95% CI: 1.037-8.360; P = 0.037) and MACE (adjusted hazard ratio 2.243 per 1 Ln U, 95% CI: 1.181-1.775; P < 0.001) adjusted for established risk factors. Repeated measurement of GDF-15 was performed in 173 survivals over 12months. Increase of GDF-15 over 12 months was associated with dilatation of left ventricle and acted as an independent predictor of subsequent all-cause death (adjusted HR = 3.164, 95% CI: 1.245-0.041; P = 0.015). In the joint model, GDF-15 was also shown to be a risk factor for all-cause death (HR = 2.749, 95% CI: 1.667-3.831; P < 0.001) and MACE (HR = 2.434, 95% CI: 1.425-3.443; P < 0.001). CONCLUSIONS: Repeated measurements of GDF-15 have promising prognostic value of the risk of all-cause death in Chinese Han patients with CHF post-myocardial infarction. GDF-15 may influence the post-myocardial infarction CHF through the path physiological pathway of myocardial remodeling.

Effect of passive cardiac containment on ventricular synchrony and cardiac function in awake dogs.

OBJECTIVE: Passive restraint of the left ventricle (LV) has been shown to have beneficial effects on acute hemodynamics and reverse remodeling in both animal and human models. The goals of this study were to test whether a left ventricular support device (LVSD) improves LV synchrony and/or affects cardiac performance. METHODS: Ten dogs were chronically instrumented to measure hemodynamics and LV volume (sonomicrometry). Congestive heart failure (CHF) was induced by repeated intracoronary microembolization via a chronically implanted coronary catheter. The LVSD was implanted after establishment of CHF in five animals, and five animals were observed as controls. All animals were then observed for 8 weeks. A mathematical model to measure LV synchrony was used to evaluate LV motion over time. RESULTS: Mean arterial pressure and LV pressures was significantly increased after LVSD therapy, and LV pressure-volume relationships were shifted leftwards, although no change was seen in ejection fraction, end-systolic elastance, or LV dP/dt versus control. There was no significant change in diastolic function in LVSD animals compared with control animals. End-diastolic volumes were reduced by 15% after 8 weeks with LVSD treatment, versus an increase of 8% in control animals (p<0.05). Synchrony was significantly improved with LVSD therapy compared with control (9% vs 76% of baseline) in 1 of 11 ventricular dimension axes (Anterior-Apex). CONCLUSIONS: LVSD therapy provided only minimal improvement in ventricular synchrony and partially improved hemodynamics. Further study into mechanisms of benefit are warranted.

Neutrophil-to-lymphocyte ratio compared to N-terminal pro-brain natriuretic peptide as a prognostic marker of adverse events in elderly patients with chronic heart failure.

BACKGROUND: The neutrophil-to-lymphocyte (N/L) ratio has been associated with poor prognosis in patients with heart failure, but it has not been compared with N-terminal pro-brain natriuretic peptide (NT-proBNP) in elderly patients with chronic heart failure (CHF). We sought to make this comparison. METHODS: A total of 1355 elderly patients with CHF were analyzed. A multivariate logistic regression model was used to analyze the variables associated with atrial fibrillation (AF). Cox regression analysis was used to assess the multivariable relationship between the N/L ratio, NT-proBNP level, and subsequent major cardiovascular events (MCE). RESULTS: In the multiple logistic regression analysis, the N/L ratio was demonstrated as a risk factor for AF in elderly patients with CHF [odds ratio (OR): 1.079, 95% confidence interval (CI): 1.027-1.134, P = 0.003]. The median follow-up period was 18 months. In a multivariable model using tertiles of both variables, the highest tertile of the N/L ratio was significantly associated with MCE [hazard ratio (HR): 1.407, 95% CI: 1.098-1.802, P = 0.007] compared with the lowest tertile. Similarly, the highest NT-proBNP tertile was also significantly associated with MCE (HR: 1.461, 95% CI: 1.104-1.934, P = 0.008). CONCLUSIONS: In elderly patients with CHF, the N/L ratio is one of the important risk factors for AF and it is an inexpensive and readily available marker with similar independent prognostic power to NT-proBNP. The risk of MCE increases 1.407-fold when the N/L ratio is elevated to the highest tertile.