A novel AGK splicing mutation in a patient with Sengers syndrome and left ventricular non-compaction cardiomyopathy.

BACKGROUND: Sengers syndrome characterized by hypertrophic cardiomyopathy is an extremely rare genetic disorder. Sengers syndrome associated with left ventricular non-compaction (LVNC) has not been described. METHODS: Genetic testing was used to identify candidate AGK variants in the proband. The predicted molecular structures were constructed by protein modeling. Exon skipping caused by the identified splicing mutations was verified by in silico analyses and in vitro assays. The genotypic and phenotypic features of patients with AGK splicing mutations were extracted by a systematic review. RESULTS: The proband was characterized by Sengers syndrome and LVNC and caused by a novel compound heterozygous AGK splicing mutation. This compound mutation simultaneously perturbed the protein sequences and spatial conformation of the acylglycerol kinase protein. In silico and in vitro analyses demonstrated skipping of exons 7 and 8 and premature truncation as a result of exon 8 skipping. The systematic review indicated that patients with an AGK splicing mutation may have milder phenotypes of Sengers syndrome. CONCLUSIONS: The genotypic and phenotypic spectrums of Sengers syndrome have been expanded, which will provide essential information for genetic counseling. The molecular mechanism in AGK mutations can offer insights into the potential targets for treatment. IMPACT: First description of a child with Sengers syndrome and left ventricular non-compaction cardiomyopathy. A novel pathogenic compound heterozygous splicing mutation in AGK for Sengers syndrome was identified. The identified mutations led to exons skipping by in silico analyses and in vitro assays.

Fusarium solani G6, a novel vitexin-producing endophytic fungus: characterization, yield improvement and osteoblastic proliferation activity.

The study aimed to characterize a novel vitexin-producing endophytic fungus Fusarium solani G6 from Cajanus cajan, improve its capability for producing vitexin and evaluate its osteoblastic proliferation activity. A total of 153 endophytic fungi, classified into 6 genera, were isolated from C. cajan. Among them, only one strain, endophyte G6 identified as Fusarium solani, was found to produce vitexin. After the optimization of fermentation conditions, the highest vitexin yield (18.72 mg/L) for the strain was observed in PDB liquid medium containing 20.54 g/L of glucose and 8.90 g/L of ammonium sulfate, at an initial medium pH of 5.1 and at 28 °C for 6 days of cultivation. Moreover, the fungal vitexin exhibited notable osteoblastic proliferation stimulating activity. A novel vitexin-producing endophytic fungus F. solani G6 was characterized from C. cajan for the first time. The findings highlighted its potential use for large-scale production of vitexin and might have a promising use as therapeutic agent for osteoporosis.

circRNA on animal skeletal muscle development regulation.

Circular RNA (circRNA) is a type of closed circular RNA molecules formed by reverse splicing, which exists widely in organisms and has become a research hotspot in non-coding RNAs in recent years. Skeletal muscle plays the role of coordinating movement and maintaining normal metabolism and endocrine in organisms. With the development of sequencing and bioinformatics analysis technology, the functions and regulation mechanisms of circRNAs in skeletal muscle development have been gradually revealed. In this review, we summarize the types of molecular regulatory mechanisms, the classical research ideas and the functional research methods of circRNAs, and the research progress of circRNAs involved in normal development of skeletal muscle and regulation of skeletal muscle disease, in order to provide a reference to further study of the genetic mechanisms of circRNAs in the regulation of skeletal muscle development.

Simultaneous pre-concentration and separation on simple paper-based analytical device for protein analysis.

In this work, fast isoelectric focusing (IEF) was successfully implemented on an open paper fluidic channel for simultaneous concentration and separation of proteins from complex matrix. With this simple device, IEF can be finished in 10 min with a resolution of 0.03 pH units and concentration factor of 10, as estimated by color model proteins by smartphone-based colorimetric detection. Fast detection of albumin from human serum and glycated hemoglobin (HBA1c) from blood cell was demonstrated. In addition, off-line identification of the model proteins from the IEF fractions with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was also shown. This PAD IEF is potentially useful either for point of care test (POCT) or biomarker analysis as a cost-effective sample pretreatment method.

Carrier ampholyte-free isoelectric focusing on a paper-based analytical device for the fractionation of proteins.

Isoelectric focusing plays a critical role in the analysis of complex protein samples. Conventionally, isoelectric focusing is implemented with carrier ampholytes in capillary or immobilized pH gradient gel. In this study, we successfully exhibited a carrier ampholyte-free isoelectric focusing on paper-based analytical device. Proof of the concept was visually demonstrated with color model proteins. Experimental results showed that not only a pH gradient was well established along the open paper fluidic channel as confirmed by pH indicator strip, the pH gradient range could also be tuned by the catholyte or anolyte. Furthermore, the isoelectric focusing fractions from the paper channel can be directly cut and recovered into solutions for post analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. This paper-based isoelectric focusing method is fast, cheap, simple and easy to operate, and could potentially be used as a cost-effective protein sample clean-up method for target protein analysis with mass spectrometry.

Remarkable enhancement of flavonoid production in a co-cultivation system of Isatis tinctoria L. hairy root cultures and immobilized Aspergillus niger.

The dried roots of Isatis tinctoria L. are highly traded in the pharmaceutical industry due to their notable anti-influenza efficacy. For the first time, I. tinctoria hairy root cultures (ITHRCs) were co-cultured with two immobilized live GRAS (Generally Recognized as Safe) fungi, i.e. Aspergillus niger and Aspergillus niger, for the elevated production of pharmacologically active flavonoids. Immobilized A. niger (IAN) was exhibited as the superior elicitor in the plant-fungus co-cultivation system. The highest flavonoid production (3018.31 ± 48.66 µg/g DW) were achieved in IAN-treated ITHRCs under the optimal conditions of IAN spore concentration ca.104 spores/mL, temperature 30 °C, initial pH value of media 7.0 and time 72 h, which remarkably increased 6.83-fold relative to non-treated control (441.91 ± 7.35 µg/g DW). Also, this study revealed that IAN elicitation could trigger the sequentially transient accumulation of signal molecules and intensify the oxidative stress in ITHRCs, which both contributed to the up-regulated expression of associated genes involved in flavonoid biosynthetic pathway. Moreover, IAN could be reused at least five cycles with satisfactory performance. Overall, the coupled culture of IAN and ITHRCs is a promising and effective approach for the enhanced production of flavonoids, which allows for the improved applicability of these valuable compounds in pharmaceutical fields.

Ultraviolet radiation for flavonoid augmentation in Isatis tinctoria L. hairy root cultures mediated by oxidative stress and biosynthetic gene expression.

Search of cost-effective strategies that can enhance the accumulation of phytochemicals of pharmaceutical interest in plant in vitro cultures is an essential task. For the first time, Isatis tinctoria L. hairy root cultures were exposed to ultraviolet radiation (ultraviolet-A, ultraviolet-B, and ultraviolet-C) in an attempt to promote the production of pharmacologically active flavonoids. Results showed that the maximum flavonoid accumulation (7259.12 ±â€¯198.19 µg/g DW) in I. tinctoria hairy root cultures treated by 108 kJ/m2 dose of UV-B radiation increased 16.51-fold as compared with that in control (439.68 ±â€¯8.27 µg/g DW). Additionally, antioxidant activity enhancement and cell wall reinforcement were found in the treated I. tinctoria hairy root cultures, indicating the positive-feedback responses to oxidative stress mediated by ultraviolet-B radiation. Moreover, the expression of chalcone synthase gene was tremendously up-regulated (up to 405.84-fold) in I. tinctoria hairy root cultures following ultraviolet-B radiation, which suggested chalcone synthase gene might play a crucial role in flavonoid augmentation. Overall, the present work provides a feasible approach for the enhanced production of biologically active flavonoids in I. tinctoria hairy root cultures via the simple supplementation of ultraviolet-B radiation, which is useful for the biotechnological production of these high-added value compounds to fulfil the ever-increasing demand in pharmaceutical fields.

Ultrasound Strain Elastography for Breast Lesions: Computer-Aided Evaluation With Quantifiable Elastographic Features.

OBJECTIVES: To develop and evaluate a set of quantifiable elastographic features based on ultrasound real-time strain elastography (SE) in differentiating between benign and malignant breast lesions. METHODS: The SE and conventional B-mode ultrasound images of 226 breast lesions (81 malignant, 145 benign) were obtained from 226 consecutive women. By using a computer-aided tool, four elastographic features (elasticity score, lesion stiffness degree, lesion-to-fat strain ratio, and elastography-to-B-mode lesion area ratio) were respectively calculated and evaluated. Histopathologic results were used as the reference standard. B-mode Breast Imaging Reporting and Data System categorization was used to compare the performances between B-mode ultrasound and SE. Sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic curve analyses were performed to evaluate the diagnostic performances for three data sets (conventional B-mode ultrasound alone, SE features alone, combined SE features). RESULTS: Quantifiable SE features for malignant lesions all showed significantly higher values than those for benign lesions (all P < .001). The evaluation with any individual SE feature significantly improved the specificity in breast lesion differentiation compared with B-mode ultrasound (all P <.001). The logistic regression model combing SE features significantly improved the diagnostic performance compared with B-mode US, with significantly increased specificity (95.2% versus 54.5%; P < .001) and area under the receiver operating characteristic curve (0.988 versus 0.921, P < .001). CONCLUSIONS: Computer-aided tool with SE provided further elasticity information for breast characterization. Evaluation using quantifiable SE features showed better diagnostic performance than conventional B-mode ultrasound in breast lesion differentiation.

Production of Laccase by a New Myrothecium verrucaria MD-R-16 Isolated from Pigeon Pea [Cajanus cajan (L.) Millsp.] and its Application on Dye Decolorization.

The present study was conducted to screen a laccase-producing fungal endophyte, optimize fermentation conditions, and evaluate the decolorization ability of the laccase. A new fungal endophyte capable of laccase-producing was firstly isolated from pigeon pea and identified as Myrothecium verrucaria based on a ITS-rRNA sequences analysis. Meanwhile, various fermentation parameters on the laccase production were optimized via response surface methodology (RSM). The optimal fermentation conditions were a fermentation time of five days, temperature 30 °C and pH 6.22. Laccase activity reached 16.52 ± 0.18 U/mL under the above conditions. Furthermore, the laccase showed effective decolorization capability toward synthetic dyes (Congo red, Methyl orange, Methyl red, and Crystal violet) in the presence of the redox mediator ABTS, with more than 70% of dyes decolorizing after 24 h of incubation. Additionally, the activity of laccase was relatively stable with pH (4.5-6.5) and a temperature range of 35-55 °C. Therefore, the high laccase production of the strain and the new fungal laccase could provide a promising alterative approach for industrial and environmental applications.

The relationship between HbA1c and ultrasound plaque textures in atherosclerotic patients.

OBJECTIVE: Diabetes mellitus (DM) is associated to the morphological and componential characteristics of atheromatous plaques. It has proven that plaque textures are related to plaque components and beneficial for atherosclerotic risk stratification. The aim of this study is to compare plaque textures in patients with and without DM, and examine the relationship between HbA1c levels and the ultrasound plaque textures in atherosclerotic patients. METHODS: A total of 136 participants (among them 66 are diabetic and 70 are non-diabetic) suffering from carotid plaques were included. About 300 texture features were extracted from the ultrasound images of plaques using the algorithms of histogram, absolute gradient, run-length matrix, gray-level co-occurrence matrix, autoregressive model and wavelet transform, respectively. Thirty optimal features were selected by the Fisher coefficient and the mutual information measure. The most discriminating feature (MDF) was obtained from the linear discriminant analysis for the optimal features. Linear regression model was performed to investigate the relationship between HbA1c and MDF. The receiver operating characteristics (ROC) curve was further developed to validate the relation between the estimated HbA1c (models output) and diabetes status. RESULTS: A total of 12 texture features showed statistical difference between patients with and without DM. The MDF was significant higher in non-diabetic patients (0.326 ± 0.049) than diabetic patients (-0.346 ± 0.052) (p < 0.001). The optimal regression model (r = 0.348, p < 0.001) for HbA1c included a constant (p < 0.001) and the MDF (p < 0.001). The areas under ROC curve used to estimate HbA1c was 0.828. CONCLUSIONS: The results indicate that there is a quantitative relationship between the HbA1c levels and plaque textures in ultrasonic images of atherosclerotic patients, which may suggest that texture analysis of the ultrasonic image of plaque is a promising method for evaluating the cardiovascular risk caused by DM in patients with plaques.

Damage to Trichothecium roseum caused by sodium silicate is independent from pH.

Trichothecium roseum is one of the most important postharvest pathogens in arid and semiarid regions. Sodium silicate (NaSi) and environmental pH have significant inhibitory effects on fungal growth. However, no study has addressed the relationship of NaSi and pH in combination and the effects on T. roseum. In this work, we showed that spore germination, germ tube elongation, and mycelial growth of T. roseum were significantly inhibited by various NaSi concentrations, which had corresponding increasing pHs. Furthermore, these NaSi solutions showed a much greater impact than did pH treatments alone. The pathogenicity of NaSi-treated conidia on a model assay (conidia-inoculated apple fruit) was dramatically reduced, whereas no changes of pathogenicity were evident for the corresponding pH (various sodium hydroxide (NaOH) solutions) treatments. Fluorescent microscopy, using propidium iodide staining, showed damage of the plasma membranes of T. roseum conidia treated with both NaSi and NaOH, although the damage was more severe with NaSi. Leakage of proteins and sugars was significantly higher in NaSi-treated and NaOH-treated conidia than in untreated controls. In addition, serious damage was observed in the conidia exposed to NaSi for longer periods of time. Ultrastructural observations showed that treatment with either NaSi or NaOH caused a plasmolysis state and disorganized organelles. Taken together the results show that NaSi has inhibitory effects on T. roseum and that the inherent higher pH of NaSi solutions of higher concentrations simply acts as an enhancer of the inhibitory effects of NaSi.

Repetitive infusion of levosimendan in patients with chronic heart failure: a meta-analysis.

BACKGROUND: Repetitive or intermittent levosimendan infusion is gradually becoming more commonly considered for patients with advanced chronic heart failure. However, previous randomized controlled studies (RCTs) reported conflicting results on the effects of levosimendan when administered repetitively. The aim of this meta-analysis was to generate up-to-date evidence to assess the effect of levosimendan in this group of patients. MATERIAL AND METHODS: A literature review identified 8 qualified studies. A meta-analysis was performed to assess mortality and left ventricular ejection fraction (LVEF). RESULTS: Use of levosimendan contributed to significantly reduced mortality at the end of mid-term follow-up. The mortality rates in levosimendan and control group were 23 of 226 (10.2%) and 53 of 198 (26.8%), respectively (RR: 0.40, 95%CI: 0.26-0.63, P<0.0001). The trend of significantly decreased mortality was observed in levosimendan vs. placebo subgroup (RR: 0.28, 95%CI: 0.15-0.54, P=0.0001, I2=0%) but not in levosimendan vs. dobutamine, PGE1, or furosemide subgroup (p=0.19, p=0.64 and p=0.25, respectively). Levosimendan also contributed to significantly improved LVEF improvement at the end of follow-up (mean difference: 3.69%, 95CI: 0.92-6.45%, p=0.009). CONCLUSIONS: Intermittent or repetitive levosimendan infusion might be a promising strategy to reduce mortality and improve LVEF in patients with advanced chronic, but not necessarily acutely decompensated, heart failure to maintain disease stability.

[Structure and function of insulin-like growth factor acid-labile subunits in mammalian homologues].

Insulin-like growth factors (IGFs) act as a critical signaling pathway in animals and play significant roles in body growth, development, and occurrence and progression of animal diseases. In the past, structural and functional studies of ligands, receptors and even specific binding proteins in the IGFs system have been extensively investigated. However, the functional study of insulin-like growth factor acid-labile subunit (IGFALS) mainly focused on the prolonging half-life of IGFs. Increasing number of studies indicated that mutations in the IGFALS DNA sequence and low expression level of IGFALS proteins can lead to growth and development retardation in animals. In this review, we summarize recent structural and functional studies of IGFALS in mammals, aiming to further identify detailed genetic mechanism of IGFALS.

Analysis of water-soluble polysaccharides in an edible medicinal plant Epimedium: method development, validation, and application.

Water-soluble polysaccharides are important constituents with evident health benefits in Epimedium. The aim of this study was to establish a specific, accurate, reproducible, and sensitive phenol-sulfuric acid method for the quantitative assay of Epimedium polysaccharides and to determine polysaccharides in Epimedium samples from Chinese markets. Galactose was adopted as the standard monosaccharide, and 486 nm was chosen as the detection wavelength. The optimal conditions for the color reaction were obtained using single factor experiments and an orthogonal test: temperature, 20 degrees C; amount of 5% phenol, 0.3 mL; amount of concentrated sulfuric acid, 3.5 mL; incubation time, 20 min; and addition sequence, phenol-sample-sulfuric acid. The colored sample solution after chromogenic reaction exhibited high stability within 2 h. The calibration curve was linear within the range 5.00-60.00 micro g/mL, and the correlation coefficient of the regression equation was 0.999. LOD and LOQ were 1.65 and 5.00 microg/mL, respectively. Recovery, intraday precision, interday precision, and accuracy were 97.43 to 103.80%, 0.73 to 3.48%, 1.21 to 2.75%, and 97.74 to 101.62%, respectively. Polysaccharides in 26 samples of Epimedium collected from different provinces of China were quantified by the proposed colorimetric method, and a large variation of contents of polysaccharides was observed among these samples.

Genetic phylogeography and maternal lineages of 18 Chinese black goat breeds.

To understand the origin and genetic phylogeography of Chinese black goats, variations of mitochondrial DNA were characterised with 394 goats from 18 breeds, including 91 new individuals from regions poorly studied until now. Comparison of a 481-bp segment revealed a total of 192 haplotypes with 141 variable sites. The haplotype and nucleotide diversities ranged from 0.782 ± 0.079 to 1.000 ± 0.020 and from 0.009 ± 0.001 to 0.045 ± 0.006, respectively, indicating a relatively high genetic diversity in Chinese black goats. Phylogenetic analyses identified five haplogroups (A, B1, B2, C and D). The dominant haplogroups A, B1 and B2 were distributed in most of breeds, while the haplogroups C and D were only presented in the breeds located in north or northwest of China. Analysis of molecular variance and multidimensional scaling plot of F ST analyses indicated no obvious geographic structure among breeds. Furthermore, the migration rates revealed that a wide range of gene flow or gene exchange occurred among breeds, which may result in the weak geographic structure of Chinese black goats. Population expansion analysis based on mismatch distribution indicated that two expansion events in Chinese black goats occurred at 10 and 28 mutational time units. Finally, our findings indicate the multiple maternal origins of Chinese black goats and more gene flow (female-mediated) which occurred during their domestic and breeding histories.

Mebendazole in the treatment of Hymenolepis nana infections in the captive ring-tailed lemur (Lemur catta), China.

The present study was conducted to evaluate the effectiveness of mebendazole in the treatment of Hymenolepis nana infection in ring-tailed lemurs (Lemur catta). Ten (L. catta) from the Chengdu Zoological Garden in China, which were naturally infected with H. nana, were treated with mebendazole (10 mg/kg for 5 days). A posttreatment fecal examination was conducted 10 and 20 days after the start of treatment. All treatments resulted in a decrease in the number of eggs per gram in the posttreatment sample compared with the pretreatment sample. Reduction of mean egg count was 97.6% and 100% on days 10 and 20, respectively. The results indicated that mebendazole has marked efficacy against H. nana infections in L. catta.

Ultrasound Stimulation of Prefrontal Cortex Improves Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice.

Increasing evidence indicates that inflammatory responses may influence brain neurochemical pathways, inducing depressive-like behaviors. Ultrasound stimulation (US) is a promising non-invasive treatment for neuropsychiatric diseases. We investigated whether US can suppress inflammation and improve depressive-like behaviors. Mice were intraperitoneally injected with lipopolysaccharide to induce depressive-like behaviors. Ultrasound wave was delivered into the prefrontal cortex (PFC) for 30 min. Depressive- and anxiety-like behaviors were evaluated through the forced swimming test (FST), tail suspension test (TST), and elevated plus maze (EPM). Biochemical analyses were performed to assess the expression of inflammatory cytokines in the PFC and serum. The results indicated that US of the PFC significantly improved depressive-like behaviors in the TST (p < 0.05) and FST (p < 0.05). Anxiety-like behaviors also improved in the EPM (p < 0.05). Furthermore, the lipopolysaccharide-mediated upregulation of IL-6, IL-1ß, and TNF-α in the PFC was significantly reduced (p < 0.05) by US. In addition, no tissue damage was observed. Overall, US of PFC can effectively improve lipopolysaccharide-induced depressive-like behaviors, possibly through the downregulation of inflammatory cytokines in the PFC. US may be a safe and promising tool for improvement of depression.

Comparative efficacy of ivermectin and levamisole for reduction of migrating and encapsulated larvae of Baylisascaris transfuga in mice.

The comparative efficacy of 2 anthelmintics (ivermectin and levamisole) against Baylisascaris transfuga migrating and encapsulated larvae was studied in mice. A total of 60 BALB/c mice inoculated each with about 1,000 embryonated B. transfuga eggs were equally divided into 6 groups (A-F) randomly. Mice of groups A and B were treated with ivermectin and levamisole, respectively, on day 3 post-infection (PI). Mice of groups A-C were killed on day 13 PI. Similarly, groups D and E were treated with ivermectin and levamisole, respectively, on day 14 PI, and all mice of groups D-F were treated on day 24 PI. The groups C and F were controls. Microexamination was conducted to count the larvae recovering from each mouse. The percentages of reduction in the number of migrating larvae recovered from group A (ivermectin) and B (levamisole) were 88.3% and 81.1%, respectively. In addition, the reduction in encapsulated larvae counts achieved by ivermectin (group D) and levamisole (group E) was 75.0% and 49.2%, respectively. The results suggested that, to a certain extent, both anthelmintics appeared to be more effective against migrating larvae than encapsulated larvae. However, in the incipient stage of infection, ivermectin may be more competent than levamisole as a larvicidal drug for B. transfuga.

Isolation and Purification of a New Bacillus Subtilis Strain from Deer Dung with Anti-microbial and Anti-cancer Activities.

OBJECTIVE: Bacillus strains are well known for their natural bioactive products that have antimicrobial and/or anti-cancer activities. Many of Bacillus' structurally unique metabolites can combat human diseases, including cancers. However, because Bacillus' metabolites are so abundant, few have been studied extensively enough to fully characterize their chemical constitutions and biological functions. METHODS: In this study, we focused on the isolation and purification of a new Bacillus strain, and determined the effects of its metabolites on bacteria and cancer cells. Our study focused on a new strain of Bacillus isolated from deer dung. Based on BLAST results, this isolate belongs to Bacillus subtilis, and therefore we named the strain Bacillus subtilis NC16. Congo red assay was used to test the cellulase activity. The inhibition zone was measured to test the antimicrobial activity. CCK-8, wound healing and flow cytometry were used to test the anti-cancer activity. RESULTS: Metabolites from Bacillus subtilis NC16 have both antimicrobial and anti-cancer activities. They can both suppress the growth of Trichoderma vride and Staphylococcus aureus, and inhibit the proliferation and promote the apoptosis of non-small cell lung cancer cell lines. CONCLUSION: Our results suggest that Bacillus subtilis NC16 can not only degrade cellulose, but its metabolites may be sources of antibiotics and anti-cancer drugs.

Two-dimensional speckle tracking echocardiography detected interventricular dyssynchrony predicts exercise capacity and disease severity in pre-capillary pulmonary hypertension.

BACKGROUND: Right ventricular (RV) intraventricular mechanical dyssynchrony detected by two-dimensional speckle tracking echocardiography (2D-STE) has been reported to be correlated with a decrease in RV contractile efficiency in pulmonary hypertension (PH) patients, while little attention has been paid to biventricular dysfunction. Therefore, we aimed to evaluate the predictive value of 2D-STE detected interventricular dyssynchrony for exercise capacity and disease severity in patients with pre-capillary PH (PcPH). METHODS: Conventional transthoracic echocardiography, 2D-STE and cardiopulmonary exercise tests (CPETs) were performed in all participants. Intra- and interventricular dyssynchrony were calculated as the standard deviation (SD) of the time intervals corrected for heart rate between QRS onset and peak longitudinal strain. Multivariate linear regression analyses were performed to identify independent predictors of peak oxygen consumption (PVO2) during the CPET. Multivariable logistical regression modeling was used to analyze the associations between interventricular dyssynchrony and risk assessment. RESULTS: Sixty-six PcPH patients were consecutively recruited (19 male and 47 female, average 35 years old). WHO functional class, N-terminal pro-brain natriuretic peptide (BNP) and body mass index were included as independent predictors in the first multivariate regression analysis of clinical data without echocardiographic parameters (Model-1, r2=0.423, P<0.001). We subsequently added conventional echocardiographic parameters and 2D-STE parameters to the clinical data, RV fractional area change (Model-2, r2=0.417, P<0.001), RV global longitudinal strain (Model-3, r2=0.454, P=0.001), RV intraventricular dyssynchrony (Model-4: r2=0.474, P<0.001) and interventricular dyssynchrony (Model-5, r2=0.483, P<0.001) were identified as independent predictors of PVO2. Interventricular dyssynchrony, calculated as the SD of the time intervals of nine segments, was independently associated with risk assessment (odd ratio 1.027, 95% CI: 1.003-1.052, P=0.03). The area under the receiver-operating characteristic curve (AUC) was 0.73 (P<0.001). CONCLUSIONS: Interventricular dyssynchrony detected by 2D-STE contributed to a better evaluation of exercise capacity and disease severity in PcPH patients.