Perceived social support and professional identity in nursing students during the COVID-19 pandemic era: the mediating effects of self-efficacy and the moderating role of anxiety.

BACKGROUND: Health professionals, including nurses, experienced heavy workloads and significant physical and mental health challenges during the coronavirus disease (COVID) 19 pandemic, which may affect career choices for those considering nursing and for nursing students. The COVID-19 pandemic is not only a period of risk, but also an occasion to redeploy the professional identity (PI) of nursing students. However, the relationship between perceived social support (PSS), self-efficacy (SE), PI and anxiety remains unclear under the background of COVID-19. This study aims to explore whether PSS has an indirect effect on PI through mediation of SE and whether the anxiety can moderate the relationship between PSS and SE in nursing students during their internship period. METHODS: An observational, national cross-sectional study was conducted following the STROBE guidelines. An online questionnaire was completed by 2,457 nursing students from 24 provinces in China during their internship during September to October 2021. Measures included Chinese translations of the Professional Identity Questionnaire for Nursing Students, the Perceived Social Support Scale, the General Self-Efficacy Scale, the 7-item Generalized Anxiety disorder scale. RESULTS: Both PSS (r = 0.46, p < 0.001) and SE (r = 0.51, p < 0.001) were positively correlated with PI. The indirect effect of PSS on PI through SE was positive (ß = 0.348, p < 0.001), with an effect of 72.7%. The results of the moderating effect analysis showed that anxiety attenuated the effect of PSS on SE. Moderation models indicated that anxiety has a weak negative moderating effect on the effect of PSS on SE (ß =-0.0308, p < 0.05). CONCLUSIONS: A better PSS and higher scores in SE were associated with PI in nursing students, and a better PSS had an indirect effect on the PI of nursing students through SE. Anxiety played a negative moderating role in the relationship between PSS and SE.

Renal-hepatic-pancreatic dysplasia-1 with a novel NPHP3 genotype: a case report and review of the literature.

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 1 (RHPD1) is a rare sporadic and autosomal recessive disorder with unknown incidence. RHPD1 is caused by biallelic pathogenic variants in NPHP3, which encode nephrocystin, an important component of the ciliary protein complex. CASE PRESENTATION: In this case report, we describe a male newborn who was confirmed by ultrasound to have renal enlargement with multiple cysts, pancreatic enlargement with cysts, and increased liver echogenicity, leading to the clinical diagnosis of RHPD. In addition, a compound heterozygous pathogenic variant, namely, NPHP3 c.1761G > A (p. W587*) and the c.69delC (p. Gly24Ala24*11) variant, was detected by WES. The patient was clinically and genetically diagnosed with RHPD1. At 34 h of life, the infant died of respiratory insufficiency. CONCLUSION: This is the first published case of RHPD1 in China. This study broadens the known range of RHPD1 due to NPHP3 pathogenic variants.

Seaweed-Derived Polysaccharides Attenuate Heat Stress-Induced Splenic Oxidative Stress and Inflammatory Response via Regulating Nrf2 and NF-κB Signaling Pathways.

With global warming, heat stress (HS) has become a worldwide concern in both humans and animals. The ameliorative effect of seaweed (Enteromorpha prolifera) derived polysaccharides (SDP) on HS-induced oxidative stress and the inflammatory response of an immune organ (spleen) was evaluated using an animal model (Gallus gallus domesticus). In total, 144 animals were used in this 4-week trial and randomly assigned to the following three groups: thermoneutral zone, HS, and HS group supplemented with 1000 mg/kg SDP. Dietary SDP improved the antioxidant capacity and reduced the malondialdehyde (MDA) of the spleen when exposed to HS, regulated via enhancing nuclear factor erythroid 2-related factor-2 (Nrf2) signaling. Furthermore, the inclusion of SDP reduced the levels of pro-inflammatory cytokines and alleviated HS-induced splenic inflammatory response by suppressing the nuclear factor-kappa B (NF-κB) p65 signaling. These findings suggest that the SDP from E. prolifera can be used as a functional food and/or feed supplement to attenuate HS-induced oxidative stress and inflammatory responses of the immune organs. Moreover, the results could contribute to the development of high-value marine products from seaweed for potential use in humans and animals, owing to their antioxidant and anti-inflammatory effects.

Balloon pulmonary angioplasty reverse right ventricular remodelling and dysfunction in patients with inoperable chronic thromboembolic pulmonary hypertension: a systematic review and meta-analysis.

OBJECTIVES: Right ventricular (RV) function is considered the major determinant of prognosis in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this meta-analysis was to evaluate RV remodelling and function following balloon pulmonary angioplasty (BPA) in patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). METHODS: We reviewed all studies evaluating RV function by cardiac magnetic resonance (CMR) and/or echocardiography pre- and post-BPA from PubMed/Medline prior to 15 December 2019. Ten (299 patients) of the 29 studies retrieved met the inclusion criteria: 5 CMR and 5 echocardiography studies. The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. RESULTS: Pooled data from CMR studies revealed BPA resulted in a significantly decreased RV end-diastolic volume index (weighted mean difference (WMD) - 28.33 ml/m2, p < 0.00001) and RV end-systolic volume index (WMD - 29.06 ml/m2, p < 0.00001) accompanied by an increased RV ejection fraction (RVEF, WMD 8.97%, p < 0.00001). Data from the echocardiography studies showed BPA resulted in decreased RV basal diameter (WMD - 0.37 cm, p = 0.0009) and an increase of RV fractional area change (WMD 5.97 %, p = 0.003), but improvements of tricuspid annular plane systolic excursion (TAPSE) and S' were not significant. CONCLUSIONS: BPA improves RVEF and decreases RV volumes in patients with inoperable CTEPH or persistent/recurrent PH after PEA. KEY POINTS: • Balloon pulmonary angioplasty improves RVEF and decreases RV volumes in patients with inoperable CTEPH or persistent/recurrent PH after PEA.

Early combined rehabilitation intervention to improve the short-term prognosis of premature infants.

BACKGROUND: To explore the clinical effect of early combined rehabilitation intervention on premature infants in the neonatal intensive care unit (NICU). METHODS: Premature infants with gestational ages less than 32 weeks or birth weights less than 1500 g were included in the present study.The participants were divided into the intervention group and control group. All infants received the current routine treatment based on the clinical guidelines, and the intervention group was additionally treated by visual and auditory stimulation, oral motor function, respiratory function and neurodevelopmental training. The following clinical outcomes were compared: durations of oxygen supplementation and indwelling gastric tube use; incidences of retinopathy of prematurity (ROP) and neonatal necrotizing enterocolitis (NEC); Sliverman scores; incidences of bronchopulmonary dysplasia (BPD) and intraventricular haemorrhage; days of hospitalization; and neurodevelopmental outcomes. Datas were analysed using the following statistical tests: the chi-square test, the independent samples or paired t test, repeated measures ANOVA, and the Wilcoxon rank sum test. RESULTS: Compared with those in the control group, premature infants in the intervention group had shorter durations of oxygen supplementation and indwelling gastric tube use, fewer hospitalization days and lower incidences of ROP, BPD, and NEC.The intervention group had lower Sliverman scores and higher Ballard neuromuscular scores than the control group. CONCLUSION: Early combined rehabilitation intervention can improve the short-term clinical outcomes of premature infants.

Impacts of anthropogenic disturbances on microbial community of coastal waters in Shenzhen, South China.

During the urbanization, human activities have brought great changes to marine biodiversity and microbial communities of coastal water. Shenzhen is a coastal city that has developed rapidly over the past four decades, but the microbial communities and metabolic potential in offshore water are still not well characterized. Here, 16S rRNA gene V4-V5 sequencing was conducted to determine the microbial components from coastal waters in twenty selected areas of Shenzhen. The results showed a significant difference on the microbial composition between the western and eastern waters. Samples from western coast had more abundant Burkholderiaceae, Sporichthyaceae, Aeromonadaceae, and Methylophilaceae compared to eastern coast, and at the genus level, Candidatus Aquiluna, Aeromonas, Arcobacter, Ottowia and Acidibacter were significantly higher in western waters. There was also a notable difference within the western sample group, suggesting the taxa-compositional heterogeneity. Moreover, analysis of environmental factors and water quality revealed that salinity, pH and dissolved oxygen were relatively decreased in western samples, while total nitrogen, total phosphorus, chemical oxygen demand, and harmful marine vibrio were significantly increased compared to eastern waters. The results suggest the coastal waters pollution is more serious in western Shenzhen than eastern Shenzhen and the microbial communities are altered, which can be associated with anthropogenic disturbances.

Identification of 16SrXXX-A Phytoplasma Associated with Salt cedar (Tamarix chinensis Lour.) witches'-broom (SCWB) in Southern Xinjiang of China.

Salt cedar is an ornamental shrub/moderate tree species native to Asia and East Europe, and grows in salt-alkali soil, desert and other dry areas, which plays an important role in wind prevention and sand fixation as well as maintaining ecological balance. Salt cedar witches'-broom (SCWB), which was extremely pernicious to Salt cedar. It was first observed and reported in Xi'an, China in 2005 (Zhao et al.2005). Witches' broom symptoms were observed on 20 out of 150 (13.3%) salt plants surveyed from the Alar region and 10 out of 86 (11.6%) plants from the Akesu region in southern of Xinjiang in May 2020. The damaged plants compared with asymptomatic plants (Fig.1A), the major symptoms included branches clustered, intersegment shorten and coarsen, giving rise to the formation of clusters (Fig.1B). Total plant DNA was extracted from phloem tissues with asymptomatic symptoms and phloem tissues with witches'-broom symptoms by a CTAB-based DNA extraction method (Green et al.1999). The 16S rRNA gene and the phytoplasma universal primers P1/P7 and rpF1/rpR1 of the rp (ribosomal protein) gene were used for Polymerase chain reaction (PCR) amplification by using the extracted plant total DNA as the template. The PCR product was used as the template and the R16F2n/R16R2 prmer was used for nested PCR amplification of the 16S rRNA gene after the amplification was completed. The results show that no product was obtained in asymptomatic plants. When DNA samples from witches'-broom symptomatic plants were used as templates, fragments with lengths 1219 bp and 1174 bp, corresponding to 16S rRNA gene and rp gene, were obtained. 16S rRNA gene was sequenced and deposited in GenBank under accession number MW447513. BLAST analysis revealed that the partial 16S rRNA sequence of the phytoplasma associated with P. aphylla witches' broom showed highest sequence identity (99.67%) to salt cedar witches' broom phytoplasma, 'Candidatus Phytoplasma tamaricis' (Accession Number: FJ432664). Phylogenetic and molecular evolutionary analyses were conducted using MEGA-X (Kumar et al., 2018). Results showed taht the SCWB and 16S rXXX group's'Candidatus Phytoplasma tamaricis', (GenBank accession: FJ432664) have the highest affinity (Fig.2A). A virtual restriction fragment length polymorphism(RFLP) was done to determinethe subgroup ( Zhao et al. 2009). The 16S rDNA sequence from the Tamarix chinensis plant showed 99.3% similarity with that of the "Candidatus Phytoplasma tamaricis" reference strain (GenBank accession: FJ432664), suggesting that the phytoplasma in this study belongs to "Candidatus Phytoplasma tamaricis"-related strain. Therefore, it can be stated that SCWB belongs to the 16S rXXX group. The partial rp sequences only shared 84.74% sequence similarity with that of 'Candidatus Phytoplasma prunorum' (MG383523) of Apple proliferation group, a known subgroup 16S rX. Blast analysis based on the partial rp sequences showed that it shares less than 90% similarity with that of any known phytoplasma (Fig 2B), we suspect that this is due to a lack of sequenced rp gene sequences for the 16S rXXX group. To our knowledge, this is the first report of Salt Cedar Witches' Broom phytoplasma in Xinjiang province, China. As a consequence, we guess the SCWB phytoplasma rp gene belongs to 16S rXXX-rp group, which is also the first report about the 16SrXXX-rp group. Because SCWB1 is the only strain in the 16S rXXX group, and it is the representative strain of the 16S rXXX-A subgroup (Zhao et al. 2009). So, the SCWB disease we found in southern Xinjiang belongs to the 16S rXXX-A subgroup.

[Effect of ginsenoside Rg_1 in delaying premature ovarian failure induced by D-gal in mice through PI3K/Akt/mTOR autophagy pathway].

The aim of this paper was to study the role of phosphoinositide 3-kinase(PI3 K), protein kinase B(Akt) and mamma-lian target of rapamycin(mTOR) in the inhibition of premature ovarian failure induced by D-galactose(D-gal) in mice model by ginsenoside Rg_1(Rg_1). Fifty-four female SPF BALB/c mice were randomly divided into PBS group, D-gal group, and Rg_1 group. In the D-gal group, D-galactose(200 mg·kg~(-1)·d~(-1)) was injected subcutaneously into the neck and back for 42 days. In the PBS group, an equal amount of phosphate buffered saline(PBS) was injected into the neck and back for 42 days. In addition to the therapy of D-gal group, Rg_1 group was given Rg_1(20 mg·kg~(-1)·d~(-1)) through intraperitoneal injection since the 15 th day for 28 days, at the same time, the D-gal group and the PBS group were also given an equal amount of PBS through intraperitoneal injection since the 15 th day for 28 days. After the treatment, the estrous cycle changes of the mice were detected, and the ovarian SA-ß-Gal staining was used to detect the changes of ovarian aging. Western blot was used to detect the changes in protein expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). Fluorescence quantitative PCR was used to detect the changes in mRNA expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). According to the findings, compared with the PBS group, the D-gal group began to show estrous cycle disorder in the 3 rd week,the ovarian SA-ß-Gal staining positive granulosa cells increased in the D-gal group, the expression of senescence marker P16~(INK4 a) increased, while the expression of autophagy signaling molecule LC3-Ⅱ decreased. After treatment with Rg_1, the positive rate of ovarian SA-ß-Gal staining in Rg_1 group decreased, the expression level of autophagy signaling molecule LC3-Ⅱ in Rg_1 group was higher than that in D-gal group, while the expression level of senescence marker P16~(INK4 a) was lower than that in D-gal group. Compared with the PBS group, the protein and mRNA expressions of PI3 K, Akt, mTOR and S6 k in the D-gal group were up-regulated, the protein expressions of Akt, mTOR and S6 k in the Rg_1 group were up-regulated, and the mRNA expressions of PI3 K and mTOR were up-regulated. After treatment with Rg_1, the protein expressions of PI3 K, Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group, while the mRNA expressions of Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group. The finding ssuggested that Rg_1 has the effect in delaying ovarian premature failure in D-gal-induced mouse models, and PI3 K/Akt/mTOR autophagy signaling pathways play an important role.

Inhibition of the RhoA/Rho-associated, coiled-coil-containing protein kinase-1 pathway is involved in the therapeutic effects of simvastatin on pulmonary arterial hypertension.

BACKGROUND: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. METHODS: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i.p.) on the first day of the study. The MCT + simvastatin group received simvastatin (2 mg/kg) daily for 4 weeks, after which pulmonary arterial pressure was measured by right heart catheterization. The protein and mRNA levels of Rho and ROCK1 were measured by immunohistochemistry, Western blot, and PCR. For in vitro experiments, human pulmonary endothelial cells were divided into seven groups: control, simvastatin, monocrotaline pyrrole (MCTP), MCTP + simvastatin, MCTP + simvastatin + mevalonate, MCTP + simvastatin + farnesyl pyrophosphate (FPP), and MCTP + simvastatin + FPP + geranylgeranyl pyrophosphate (GGPP). After 72 h exposed to the drugs, the protein and mRNA levels of RhoA and ROCK1 were measured by Western blot and PCR. RESULTS: The MCT group showed increased mean pulmonary arterial pressure, marked vascular remodeling, and increased protein and mRNA levels of RhoA and ROCK1 compared to the other groups (P < 0.05). In vitro, the MCTP group showed a marked proliferation of vascular endothelial cells, as well as increased protein and mRNA levels of RhoA and ROCK1 compared to the MCTP + simvastatin group. The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. CONCLUSIONS: Simvastatin improved vascular remodeling and inhibited the development of PAH. The effects of simvastatin were mediated by inhibition of RhoA/ROCK1. Simvastatin decreased RhoA/ROCK1 overexpression by inhibition of mevalonate, FPP, and GGPP synthesis.

Prediction of respiratory function in patients with severe scoliosis on the basis of the novel individualized spino-pelvic index.

OBJECTIVE: Our study aimed to evaluate the pulmonary function of patients with severe scoliosis after correcting standing height with spino-pelvic index (SPI). METHODS: Inclusion criteria: (1) with a coronal Cobb angle of more than 90°; (2) diagnosed as congenital (CS) or idiopathic scoliosis (IS); (3) aged between ten and 20 years; (4) with pulmonary function test (PFT) at the primary consultation. Patients with previous surgical intervention, with angular kyphosis, and with neuromuscular disease were excluded. Length of spine (LOS), height of spine (HOS), and height of pelvis (HOP) were measured on coronal films. SPI was defined as the ratio between LOS and HOP. The corrected body height was calculated: corrected body height = body height + (SPI × HOP - HOS). The PFTs included the following parameters: VCmax, FVC, FVC% predicted, FEV1, FEV1% predicted, PEF, and MVV. PFT results were recalculated using the corrected body height. RESULTS: Thirty patients were diagnosed as IS and 27 as CS with average Cobb angles of 99.88° ± 11.83 and 98.06° ± 14.27, respectively. Significant differences were observed in VCmax and FVC between IS and CS patients (P < 0.05). All the corrected PFT parameters were significantly lower than the original PFT parameters (P < 0.05). CONCLUSION: For the first time, this study proposed a method to predict pulmonary function of patients with severe scoliosis using SPI, as an age-independent parameter in normal adolescents. After body height correction, pulmonary function of patients with severe scoliosis was found to be significantly decreased, indicating that pulmonary function impairment was underestimated in patients with severe scoliosis when evaluating pulmonary function with arm span.

Long non-coding RNA MALAT1 functions as a mediator in cardioprotective effects of fentanyl in myocardial ischemia-reperfusion injury.

Long non-coding (lncRNA) MALAT1 can be increased by hypoxia or ischemic limbs. Also, downregulation of MALAT1 contributes to reduction of cardiomyocyte apoptosis. However, the functional involvement of MALAT1 in myocardial ischemia-reperfusion (I/R) injury has not been defined. This study investigated the functional involvement of lncRNA-MALAT1 in cardioprotective effects of fentanyl. HL-1, a cardiac muscle cell line from the AT-1 mouse atrial cardiomyocyte tumor lineage was pre-treated with fentanyl and generated cell model of hypoxia-reoxygenation (H/R). Relative expression of MALAT1, miR-145, and Bnip3 mRNA in cells was determined by quantitative real-time PCR. Cardiomyocyte H/R injury was indicated by lactate dehydrogenase (LDH) release and cell apoptosis. The results showed that fentanyl abrogates expression of responsive gene for H/R and induces downregulation of MALAT1 and Bnip3 and upregulation of miR-145. We found that miR-145/Bnip3 pathway was negatively regulated by MALAT1 in H/R-HL-1 cell with or without fentanyl treatment. Moreover, both MALAT1 overexpression and miR-145 knockdown reverse cardioprotective effects of fentanyl, as indicated by increase in LDH release and cell apoptosis. The reversal effect of MALAT1 for fentanyl is confirmed in cardiac ischemia/reperfusion (I/R) mice. In summary, lncRNA-MALAT1 is sensitive to H/R injury and abrogates cardioprotective effects of Fentanyl by negatively regulating miR-145/Bnip3 pathway.

Propofol protects against hepatic ischemia/reperfusion injury via miR-133a-5p regulating the expression of MAPK6.

Propofol has been found to play an important role in hepatic ischemia/reperfusion (I/R) injury with the antioxidant effects. However, the molecular mechanism of propofol in hepatic I/R injury has not been fully understood. Male Sprague-Dawley rats were randomly assigned into Sham group, hepatic I/R group, and propofol treatment group. I/R injury was attained by ischemia for 1 h and reperfusion for 2 h. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were detected. QSG-7701 cells were cultured in hypoxia condition for 15 h and then in reoxygenation condition for 6 h to imitate hypoxia/reoxygenation (H/R) injury in vitro. Real-time RT-PCR and Western blot were performed to determine the expression of miR-133a-5p and MAPK6. Luciferase reporter assay was used to determine the regulation of miR-133a-5p on MAPK6. Propofol significantly reduced the activities of serum AST and ALT induced by hepatic I/R injury in rats. Propofol increased the level of miR-133a-5p and decreased the expression of MAPK6 in vivo and in vitro. Luciferase reporter assay showed that MAPK6 was a target of miR-133a-5p. Knockdown of miR-133a-5p abrogated the effect of propofol on the upregulation of MAPK6 induced by H/R. MAPK6 overexpression promoted the cell apoptosis induced by H/R which could be attenuated by propofol. Finally, we found that miR-133a-5p reversed the protective effect of propofol in rats with hepatic I/R injury. Propofol showed protective roles for hepatic I/R injury in vivo and H/R injury in vitro, which involved with miR-133a-5p regulating the expression of MAPK6.

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH). METHOD: 194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH. RESULTS: Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = -0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = -0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan-Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001). CONCLUSION: Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

Prognostic Value of Pulmonary Artery Compliance in Patients with Pulmonary Arterial Hypertension Associated with Adult Congenital Heart Disease.

In congenital heart disease (CHD), the presence of pulmonary arterial hypertension (PAH) is associated with a poor prognosis. In this study, we aim to investigate the role of pulmonary artery compliance (Cp) in predicting the mortality of PAH associated with adult congenital heart disease (APAH-CHD). One-hundred and seventy-five patients of APAH-CHD who underwent a comprehensive clinical evaluation were included in this study. All patients were followed up in a 6-month interval and the primary end point was all cause of death. The duration of mean follow-up was 67±26 months, of which there were twenty-three death. Cp had an inverse correlation with pulmonary artery resistance (PVR), regardless of the clinical phenotype (Eisenmenger syndrome, PAH with small defect and PAH after defect correction). Patients in the lowest Cp group (Cp ≤ 0.84 mL/mmHg) had advanced WHO function class, worse exercise tolerance, liver function, and status of oxygen saturation. In univariate cox regression analysis, Cp (HR = 1.359, P < 0.001), PVR (HR = 0.972, P = 0.001), pulmonary blood flow (HR = 1.092, P = 0.001), heart rate (HR = 1.038, P = 0.028) and 6-minute walking distance (HR = 1.003, P = 0.037) were predictors of survival. After adjustment by bivariate analysis, Cp was the independent predictor. Kaplan-Meier survival curves showed that patients with Cp < 1.04 mL/mmHg had worse prognosis. In conclusion, Cp possibly reflects disease severity and decreased Cp was associated with poor prognosis in patients with APAH-CHD.

Comparative analysis on genome-wide DNA methylation in longissimus dorsi muscle between Small Tailed Han and Dorper×Small Tailed Han crossbred sheep.

OBJECTIVE: The objective of this study was to compare the DNA methylation profile in the longissimus dorsi muscle between Small Tailed Han and Dorper×Small Tailed Han crossbred sheep which were known to exhibit significant difference in meat-production. METHODS: Six samples (three in each group) were subjected to the methylated DNA immunoprecipitation sequencing (MeDIP-seq) and subsequent bioinformatics analyses to detect differentially methylated regions (DMRs) between the two groups. RESULTS: 23.08 Gb clean data from six samples were generated and 808 DMRs were identified in gene body or their neighboring up/downstream regions. Compared with Small Tailed Han sheep, we observed a tendency toward a global loss of DNA methylation in these DMRs in the crossbred group. Gene ontology enrichment analysis found several gene sets which were hypo-methylated in gene-body region, including nucleoside binding, motor activity, phospholipid binding and cell junction. Numerous genes were found to be differentially methylated between the two groups with several genes significantly differentially methylated, including transforming growth factor beta 3 (TGFB3), acyl-CoA synthetase long chain family member 1 (ACSL1), ryanodine receptor 1 (RYR1), acyl-CoA oxidase 2 (ACOX2), peroxisome proliferator activated receptor-gamma2 (PPARG2), netrin 1 (NTN1), ras and rab interactor 2 (RIN2), microtubule associated protein RP/EB family member 1 (MAPRE1), ADAM metallopeptidase with thrombospondin type 1 motif 2 (ADAMTS2), myomesin 1 (MYOM1), zinc finger, DHHC type containing 13 (ZDHHC13), and SH3 and PX domains 2B (SH3PXD2B). The real-time quantitative polymerase chain reaction validation showed that the 12 genes are differentially expressed between the two groups. CONCLUSION: In the current study, a tendency to a global loss of DNA methylation in these DMRs in the crossbred group was found. Twelve genes, TGFB3, ACSL1, RYR1, ACOX2, PPARG2, NTN1, RIN2, MAPRE1, ADAMTS2, MYOM1, ZDHHC13, and SH3PXD2B, were found to be differentially methylated between the two groups by gene ontology enrichment analysis. There are differences in the expression of 12 genes, of which ACSL1, RIN2, and ADAMTS2 have a negative correlation with methylation levels and the data suggest that DNA methylation levels in DMRs of the 3 genes may have an influence on the expression. These results will serve as a valuable resource for DNA methylation investigations on screening candidate genes which might be related to meat production in sheep.

Pulmonary Vascular Capacitance is Associated with Vasoreactivity and Long-Term Response to Calcium Channel Blockers in Idiopathic Pulmonary Arterial Hypertension.

PURPOSE: This study aimed to identify the relationship between pulmonary vascular capacitance (PVC) and vasoreactivity in patients with idiopathic pulmonary arterial hypertension (IPAH), and the value of PVC in predicting long-term response to CCB treatment. METHODS: Pulmonary vasodilator testing with inhaling iloprost was performed in 308 newly diagnosed IPAH patients. Acute vasodilator-responsive patients accepted CCBs treatment. Patients who benefit from long-term CCB were defined as those being in World Health Organization (WHO) functional class II or I after at least 1 year on CCB monotherapy. RESULTS: PVC had significant correlations with WHO function class, 6-min walk distance, mean pulmonary arterial pressure, and pulmonary vascular resistance (r = -0.363, p < 0.001; r = 0.333, p < 0.001; r = -0.514, p < 0.001; r = -0.739, p < 0.001). Thirty-five acute vasodilator-responsive IPAH patients (11.4 %) displayed less severe disease and a higher baseline PVC (1.5 ± 0.6 vs. 1.1 ± 0.7 ml/mmHg, p = 0.003). During acute vasodilator testing, PVC increased significantly by mean of 79 ± 48 % and reached to a higher absolute value of 2.6 ± 1.5 ml/mmHg compared with non-responsive patients (1.4 ± 1.5 ml/mmHg, p < 0.001). Furthermore, PVC increased more during acute vasodilator testing in the 24 patients who benefit from long-term CCB treatment (1.4 ± 1.3 vs. 0.5 ± 0.4 ml/mmHg, p = 0.004). The OR of increased PVC during vasodilator testing for predicting patients with long-term response to CCB was 1.24 (95 % CI 1.02-1.50, p = 0.031) as assessed by multivariable logistic regression analysis. CONCLUSIONS: PVC was higher in acute vasodilator-responsive IPAH patients and may be a predictor of long-term response to CCBs therapy.

Platelet distribution width and mean platelet volume in idiopathic pulmonary arterial hypertension.

BACKGROUND: Previous studies have demonstrated that platelet activation occurs in patients with pulmonary arterial hypertension (PAH). Mean platelet volume (MPV) and platelet distribution width (PDW) are two markers of platelet activation, and have recently been recognised as risk predictors of cardiovascular diseases. This study aimed to investigate whether MPV and PDW would be useful to reflect disease severity and predict prognosis in idiopathic PAH (IPAH). METHODS: MPV and PDW levels were measured in 82 IPAH patients without antiplatelet or anticoagulant treatment on admission and 82 healthy controls. Concurrent collected data included clinical, haemodynamic and biochemical variables. All patients were followed-up from the date of blood testing. The endpoint was all-cause mortality. RESULTS: MPV and PDW were significantly higher in patients with IPAH than in age and sex-matched control subjects (11.4±0.9fl vs. 10.3±0.9fL and 14.3±2.9% vs. 11.9±1.9%, respectively; p=0.000). Pearson's correlation analysis revealed that MPV and PDW correlated positively with right ventricular systolic pressure, mean pulmonary arterial pressure and pulmonary vascular resistance. After a mean follow-up of 14±8 months, 12 patients died of right heart failure. Receiver operating characteristic analysis showed that MPV and PDW could not predict all-cause mortality. Multivariate Cox regression analysis suggested that right/left ventricular end-diastolic diameter ratio and NT-proBNP were independent predictive parameters of all-cause mortality. CONCLUSIONS: Our results suggest that MPV and PDW were elevated in patients with IPAH. They could partly reflect disease severity, but did not predict prognosis.

Red blood cell distribution width predicts survival in patients with Eisenmenger syndrome.

BACKGROUND: Previous studies identified an independent relationship between red blood cell distribution width (RDW) and prognosis in patients with pulmonary hypertension of mixed etiologies and idiopathic pulmonary arterial hypertension. This study aimed to investigate the significance of RDW for predicting survival in patients with Eisenmenger syndrome (ES). METHODS: We retrospectively reviewed the clinical records and collected baseline data for patients newly diagnosed with ES in our hospital between January 2005 and October 2009. Follow-up data were collected periodically using a specifically designed network database until December 31, 2012. The end point was all-cause death. RESULTS: A total of 109 patients with ES were included in the study. Twenty-one patients (19.3%) died during a median follow-up period of 4.2 years (interquartile range 3.7-5.0 years). Baseline RDW was significantly correlated with mixed venous oxygen saturation (r=-0.286, p=0.003), arterial oxygen saturation (r=-0.423, p<0.001), mean pulmonary arterial pressure (r=0.271, p=0.004) and total pulmonary resistance (r=0.465, p<0.001). The 1-, 3- and 5-year survival rates for all 109 patients were 94%, 87% and 78%, respectively. Kaplan-Meier analysis showed that patients with RDW ≥13.9% had a lower survival rate than patients with RDW <13.9% (p=0.001). Multivariate Cox regression analysis showed that RDW was an independent prognostic marker in ES, with a hazard ratio of 1.162 (95% CI 1.036-1.302; p=0.010). CONCLUSIONS: Baseline RDW correlates with hemodynamics and is an independent prognostic marker in ES.

Elevated plasma YKL-40 as a prognostic indicator in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Pulmonary vascular remodelling and inflammation have been implicated in pulmonary arterial hypertension (PAH). YKL-40, a marker of tissue remodelling and inflammation, has recently been recognized as a risk predictor of cardiovascular and inflammatory diseases. The study aimed to investigate a potential role of YKL-40 in predicting prognosis in idiopathic PAH (IPAH). METHODS: Plasma YKL-40 levels were measured in 82 IPAH patients without current or previous PAH-specific treatment during right heart catheterization and in 54 healthy volunteers. Concurrent data included clinical, haemodynamic and biochemical variables. RESULTS: Plasma YKL-40 levels were increased in IPAH patients compared with control subjects (median, interquartile range: IPAH: 24.90, 17.68-39.78 ng/mL; controls: 16.58, 14.20-19.64 ng/mL; P < 0.001). YKL-40 levels correlated with cardiac index (r = -0.244, P = 0.027) and N-terminal pro-brain natriuretic peptide (NT-proBNP, r = 0.263, P = 0.017). After a median follow-up of 578 days, YKL-40 outperformed NT-proBNP, uric acid, and 6-min walk distance in receiver operating characteristic (ROC) analyses in predicting both clinical worsening (area under the curve (AUC) 0.681) and death (AUC 0.717). Compared with patients with YKL-40 below the ROC-derived cut-off point (24.5 ng/mL), the high YKL-40 group showed higher pulmonary vascular resistance and serum uric acid levels, and showed more clinical worsening events and deaths in Kaplan-Meier analyses. Plasma YKL-40 was independently associated with clinical worsening in univariate and multivariate Cox analyses (all P < 0.05). CONCLUSIONS: Plasma YKL-40 might serve as a promising indicator of disease severity and prognosis in patients with IPAH.

Pulmonary function differences in patients with chronic right heart failure secondary to pulmonary arterial hypertension and chronic left heart failure.

BACKGROUND: Pulmonary abnormalities are found in both chronic heart failure (CHF) and pulmonary arterial hypertension (PAH). The differences of pulmonary function in chronic left heart failure and chronic right heart failure are not fully understood. MATERIAL AND METHODS: We evaluated 120 patients with stable CHF (60 with chronic left heart failure and 60 with chronic right heart failure). All patients had pulmonary function testing, including pulmonary function testing at rest and incremental cardiopulmonary exercise testing (CPX). RESULTS: Patients with right heart failure had a significantly lower end-tidal partial pressure of CO2 (PetCO2), higher end-tidal partial pressure of O2 (PetO2) and minute ventilation/CO2 production (VE/VCO2) at rest. Patients with right heart failure had a lower peak PetCO2, and a higher peak dead space volume/tidal volume (VD/VT) ratio, peak PetO2, peak VE/VCO2, and VE/VCO2 slope during exercise. Patients with right heart failure had more changes in ∆PetCO2 and ∆VE/VCO2, from rest to exercise. CONCLUSIONS: Patients with right heart failure had worse pulmonary function at rest and exercise, which was due to severe ventilation/perfusion (V/Q) mismatching, severe ventilation inefficiency, and gas exchange abnormality.