Radiotherapy combined with anti-PD-1 and TKI for primary cardiac angiosarcoma considering the joint assessment of TLSs and PD-L1: a case report.

BACKGROUND: Primary cardiac angiosarcoma(PCA) has a low incidence rate and poor prognosis. Currently, no unified clinical treatment standards are available. CASE PRESENTATION: We report the case of a 48-year-old man presenting chest tightness, breathlessness, and dyspnea. Imaging and postoperative histopathologic studies confirmed PCA and that the tumor had invaded the entire right atrium. The patient developed progressive disease (PD) during postoperative radiotherapy. We used immunotherapy combined with targeted therapy based on the results of molecular profile and evaluation of tertiary lymphoid structures (TLSs) and programmed cell death-ligand 1 (PD-L1). After treatment, the metastatic lymph nodes of the patient were reduced to a certain extent, indicating that combination therapy was effective. CONCLUSION: To the best of our knowledge, this is the first report of radiotherapy combined with anti-PD-1 and tyrosine kinase inhibitors(TKI) for PCA. In addition, this is the first report on immunotherapy for PCA based on new evaluation methods, including TLSs, PD-L1, and genomic profile.

Systematic assessment of the antifungal mechanism of soil fumigant methyl isothiocyanate against Fusarium oxysporum.

Fusarium oxysporum is an important phytopathogenic fungus, it can be controlled by the soil fumigant methyl isothiocyanate (MITC). However, the antimicrobial mechanism of MITC against F. oxysporum, especially at the transcriptional level, is still unclear. In this experiment, the antimicrobial mechanism of MITC against F. oxysporum was investigated. Our results indicated that when F. oxysporum was exposed to 6 mg/L MITC for 12 h, the inhibitory rate of MITC on F. oxysporum was 80%. Transmission electron microscopes showed that the cell wall and membrane of F. oxysporum had shrunk and folded, vacuoles increased, and mitochondria swelled and deformed. In addition, the enzyme activity of F. oxysporum treated with MITC showed a decrease of 32.50%, 8.28% and 74.04% in catalase, peroxidase and superoxide dismutase, respectively. Transcriptome sequencing of F. oxysporum was performed and the results showed that 1478 differentially expressed genes (DEGs) were produced in response to MITC exposure. GO and KEGG analysis showed that the DEGs identified were involved in substance and energy metabolism, signal transduction, transport and catalysis. MITC disrupted cell homeostasis by influencing the expression of some key genes involved in chitin synthase and detoxification enzymes production, but F. oxysporum also protected itself by up-regulating genes involved in energy synthesis (such as upregulating acnA, CS and LSC2 in TCA). qRT-PCR data validated the reliability of transcriptome data. Our research used biochemical and genetic techniques to identify molecular lesions in the mycelia of F. oxysporum exposed to MITC, and provide valuable insights into the toxic mechanism of pathogenic fungi mediated by MITC. These techniques are also likely to be useful for rapidly screening and identifying new, environmentally-friendly soil fumigants that are efficacious against fungal pathogens.

Assessment on the stereoselective behavior of cyflumetofen to earthworms (Eisenia foetida): Degradation, bioaccumulation, toxicity mechanism, and metabolites.

In this study, environmental behavior and toxicity of cyflumetofen (CYF) enantiomers were evaluated comprehensively in a soil-earthworm system. In the earthworm (Eisenia foetida), (+)-CYF was preferentially accumulated, and acute toxicity of Rac-CYF was greater than that of (+)-CYF and (-)-CYF, indicating that the combination of CYF enantiomers increased the toxicity. As a measure of chronic toxicity, compared with (-)-CYF-treated earthworms, malondialdehyde accumulation was higher in (+)-CYF-treated earthworms, indicating a more severe oxidative stress response. In a DNA comet plot, the trailing distance in the (+)-CYF treatment was 1.97 times greater than that in the (-)-CYF-treated, revealing more severe genotoxicity with (+)-CYF. However, (-)-CYF was more likely than (+)-CYF to activate the earthworm detoxification enzyme pathway. With (+)-CYF treatment, the number of differentially expressed genes (DEGs) involved in the pathogenic pathway increased significantly, whereas with (-)-CYF-treatment, more DEGs were involved in P450 and glutathione S-transferase (GST) detoxification metabolic pathways, including high expression of the genes chi-III, GST-S-1, and GST-alpha-5. The main metabolites of the CYF enantiomers were A-2, A-12, B-1, AB-1, AB-7, and B-3, which exhibited potential ecotoxicity. In general, CYF was stereoselective in the soil-earthworm ecosystem, with (+)-CYF causing a higher genotoxicity risk than that of (-)-CYF. The study provides insight into the selective toxicity mechanisms of chiral CYF and contributes to a theoretical basis for risk assessment of low-risk pesticides.

Systematic assessment of cyflumetofen toxicity in soil-earthworm (Eisenia fetida) microcosms.

Cyflumetofen was widely applied in agriculture with its excellent acaricidal effect. However, the impact of cyflumetofen on the soil non-target organism earthworm (Eisenia fetida) is unclear. This study aimed to elucidate the bioaccumulation of cyflumetofen in soil-earthworm systems and the ecotoxicity of earthworms. The highest concentration of cyflumetofen enriched by earthworms was found on the 7th day. Long-term exposure of earthworms to the cyflumetofen (10 mg/kg) could suppress protein content and increases Malondialdehyde content leading to severe peroxidation. Transcriptome sequencing analysis demonstrated that catalase and superoxide-dismutase activities were significantly activated while genes involved in related signaling pathways were significantly upregulated. In terms of detoxification metabolic pathways, high concentrations of cyflumetofen stimulated the number of Differentially-Expressed-Genes involved in the detoxification pathway of the metabolism of glutathione. Identification of three detoxification genes (LOC100376457, LOC114329378, and JGIBGZA-33J12) had synergistic detoxification. Additionally, cyflumetofen promoted disease-related signaling pathways leading to higher disease risk, affecting the transmembrane capacity and cell membrane composition, ultimately causing cytotoxicity. Superoxide-Dismutase in oxidative stress enzyme activity contributed more to detoxification. Carboxylesterase and glutathione-S-transferase activation play a major detoxification role in high-concentration treatment. Altogether, these results contribute to a better understanding of toxicity and defense mechanisms involved in long-term cyflumetofen exposure in earthworms.

Assessment of Left Atrial Structure and Function by Echocardiography in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia with significant morbidity and mortality. Exacerbated by the aging population, the prevalence of AF is gradually increasing. Accurate evaluation of structure and function of left atrium (LA) has important prognostic significance in patients with AF. Echocardiography is the imaging technique of first choice to assess LA structure and function due to its better availability, accessibility and safety over cardiac computed tomography and cardiac magnetic resonance. Therefore, the aim of this review is to summarize the recent research progress of evaluating LA size by three-dimensional echocardiography and LA function by speckle tracking echocardiography (STE) in predicting the occurrence and recurrence of AF and determining the risk of stroke in AF. In addition, we summarized the role of traditional echocardiography in detecting AF patients that are at high risk of heart failure or cardiovascular death.

Quality assessment of Fritillariae cirrhosae using portable NIR spectrometer.

This paper mainly focuses on the feasibility of rapidly identifying Fritillariae cirrhosae varieties, distinguishing its authenticity and detecting its components by using a portable near infrared (NIR) spectrometer. Five different varieties of Fritillariae cirrhosae, five common counterfeits and two main components (ethanol-soluble extractives and total alkaloids) were studied. The reference values of ethanol-soluble extractives were determined by hot dip method and the reference value of total alkaloid was determined by ultraviolet-visible spectrophotometry (UV-Vis). Linear discriminant analysis (LDA) algorithm was used to identify the sources of different varieties of Fritillariae cirrhosae and the common counterfeits of Fritillariae cirrhosae, respectively. As a result, the best models seemed to be effective, with accuracy of the two models' prediction sets reaches 83.33% and 90.91%, respectively. The partial least squares regression (PLSR) algorithm was used to relate the sample spectra with the reference values of ethanol-soluble extractives and total alkaloid content. Coefficient of determination of prediction (R2p) and root mean square errors of prediction (RMSEP) obtained were 0.8562 and 0.3911; 0.6917 and 0.0117, for ethanol-soluble extractives and total alkaloid content, respectively. The results showed that the portable NIR spectrometer could evaluate the quality of Fritillariae cirrhosae with high efficiency and practicability.

Quantitative assessment of the association between rs2046210 at 6q25.1 and breast cancer risk.

Genome-wide association studies (GWAS) have identified several genetic susceptibility loci for breast cancer (BC). One of them, conducted among Chinese women, found an association of rs2046210 at 6q25.1 with the risk of BC recently. Since then, numerous association studies have been carried out to investigate the relationship between this polymorphism and BC risk in various populations. However, these have yielded contradictory results. We therefore performed a meta-analysis to clarify this inconsistency. Overall, a total of 235003 subjects based on 13 studies were included in our study. Significantly increased BC risk was detected in the pooled analysis [allele contrast: OR = 1.13, 95%CI = 1.10-1.17, P(Z) <10(-5), P(Q) <10(-4); dominant model: OR = 1.21, 95%CI = 1.14-1.27, P(Z) <10(-5), P(Q) <10(-4); recessive model: OR = 1.18, 95%CI = 1.12-1.24, P(Z) <10(-5), P(Q) = 0.04]. In addition, our data revealed that rs2046210 conferred greater risk in estrogen receptor (ER)-negative tumors [OR = 1.27, 95%CI = 1.15-1.40, P(Z) <10(-5), P(Q) <10(-4)] than in ER-positive ones [OR = 1.18, 95%CI = 1.09-1.28, P(Z) <10(-4), P(Q) = 0.0003]. When stratified by ethnicity, significant associations were found in Caucasian and Asian populations, but not detected among Africans. There was evidence of heterogeneity (P<0.05), however, the heterogeneity largely disappeared after stratification by ethnicity. The present meta-analysis demonstrated that the rs2046210 polymorphism may be associated with increased BC susceptibility, but this association varies in different ethnicities.

Quantitative assessment of the effect of LRRK2 exonic variants on the risk of Parkinson's disease: a meta-analysis.

Leucine-rich repeat kinase 2 (LRRK2, PARK8) gene has attracted considerable attention since the variants in this gene are recognized as the most common cause of Parkinson's disease (PD) so far. A number of association studies concerning variants of LRRK2 gene and PD susceptibility have been conducted in various populations. However, some results were inconclusive. To derive a more precise estimation of the relationship between LRRK2 and genetic risk of PD, we performed a comprehensive meta-analysis which included 27,363 cases and 29,741 controls from 61 published case-control studies. Totally, the effect of five LRRK2 variants all within the coding regions, i.e. G2019S, G2385R, R1628P, P755L and A419V, were evaluated in the meta-analysis using fixed effect model or random effects model if heterogeneity existed. There were genetic associations between four variants (G2019S, G2385R, R1628P and A419V) and increased PD risk, while there was no evidence of statistically significant association between P755L and PD. Publication bias and heterogeneity were absent in most analyses. Within its limitations, this meta-analysis demonstrated that the G2019S, G2385R, R1628P and A419V variations are risk factors associated with increased PD susceptibility. However, these associations vary in different ethnicities.

Assessment of bacterial communities and characterization of lead-resistant bacteria in the rhizosphere soils of metal-tolerant Chenopodium ambrosioides grown on lead-zinc mine tailings.

Bacterial communities in the rhizosphere soils of metal tolerant and accumulating Chenopodium ambrosioides grown in highly and moderately lead-zinc mine tailings contaminated-soils as well as the adjacent soils with low metal contamination were characterized by using cultivation-independent and cultivation techniques. A total of 69, 73, and 83 bacterial operational taxonomic units (OTUs) having 84.8-100% similarity with the closest match in the database were detected among high, moderate, and low-contamination soil clone libraries, respectively. These OTUs had a Shannon diversity index value in the range of 4.06-4.30. There were 9, 10, and 14 bacterial genera specific to high, moderate, and low metal-contaminated soil clone libraries, respectively. Phylogenetic analysis showed that the Pb-resistant isolates belonged to 8 genera. Pseudomonas and Arthrobacter were predominant among the isolates. Most of the isolates (82-86%) produced indole acetic acid and siderophores. More strains from the highly metal-contaminated soil produced 1-aminocyclopropane-1-carboxylate deaminase than the strains from the moderately and lowly metal-contaminated soils. In experiments involving canola grown in quartz sand containing 200 mg kg(-1) of Pb, inoculation with the isolated Paenibacillus jamilae HTb8 and Pseudomonas sp. GTa5 was found to significantly increase the above-ground tissues dry weight (ranging from 19% to 36%) and Pb uptake (ranging from 30% to 40%) compared to the uninoculated control. These results show that C. ambrosioides harbor different metal-resistant bacterial communities in their rhizosphere soils and the isolates expressing plant growth promoting traits may be exploited for improving the phytoextraction efficiency of Pb-polluted environment.

Quantitative assessment of the effect of ABCA1 R219K polymorphism on the risk of coronary heart disease.

In the past decade, a number of case-control studies have been conducted to investigate the relationship between the ATP-binding cassette transporter A1 (ABCA1) R219K polymorphism and coronary heart disease (CHD). However, the results have been inconclusive. The purpose of the present study is to investigate whether this polymorphism confers significant susceptibility to CHD using a meta-analysis. PubMed, Embase and CNKI database were searched to get the genetic association studies. Then data were extracted. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. Moreover, subgroup and sensitive analysis were performed. In total, 9,437 cases and 16,270 controls were involved in the meta-analysis. The K219 was significantly associated with CHD (OR = 0.80, 95% CI 0.69-0.92, P(Z) = 0.001). However, significant heterogeneity was present. Further subgroup analysis suggested ethnicity explained much heterogeneity. In Asians, K219 showed a strong protective effect and the pooled OR was 0.69 (95% CI 0.55-0.86 P(Z) = 0.0009). While in Caucasians the result was not significant (OR = 0.87, 95% CI 0.73-1.04, P(Z) = 0.12). In conclusion, our results indicate that the ABCA1 R219K polymorphism is a protective factor of CHD in Asians, but not in Caucasians.

A cross-national comparative study of orphan drug policies in the United States, the European Union, and Japan: towards a made-in-China orphan drug policy.

Rare diseases can severely impact patient life quality as well as impose a serious burden on society. But research and development for drugs to treat these disorders has stagnated because of lack of demand, insufficient knowledge of pathophysiological mechanisms, and too few patients for clinical trials. In several countries--the United States, the EU, and Japan--specific legislation has been enacted to encourage pharmaceutical companies to expedite the development of drugs for rare diseases, orphan drugs, and to assure access to them. We analyze the strengths and weaknesses of the incentives in these laws and describe the status of rare diseases in China. We offer some recommendations for orphan drug legislation in China, based on local research on rare diseases.

Clinical value of stereoscopic three-dimensional echocardiography in assessment of atrial septal defects: feasibility and efficiency.

Stereoscopic three-dimensional echocardiography(S-3DE) is a novel displaying technology based on real-time 3-dimensional echocardiography (RT-3DE). Our study was to evaluate the feasibility and efficiency of S-3DE in the diagnosis of atrial septal defect (ASD) and its use in the guidance for transcatheter ASD occlusion. Twelve patients with secundum ASD underwent RT-3DE examination and 9 of the 12 were subjected to transcatheter closure of ASD. Stereoscopic vision was generated with a high-performance volume renderer with red-green stereoscopic glasses. S-3DE was compared with standard RT-3D display for the assessment of the shape, size, and the surrounding tissues of ASD and for the guidance of ASD occlusion. The appearance rate of coronary sinus and the mean formation time of the IVC, SVC were compared. Our results showed that S-3DE could measure the diameter of ASD accurately and there was no significant difference in the measurements between S-3DE and standard 3D display (2.89+/-0.73 cm vs 2.85+/-0.72 cm, P>0.05; r=0.96, P<0.05). The appearance of coronary sinus for S-3DE was higher as compared with the standard 3D display (93.3% vs 100%). The mean time of the IVC, SVC for S-3DE monitor was slightly shorter than that of the standard 3D display (11.0+/-3.8 s vs 10.3+/-3.6 s, P>0.05). The mean completion time of interventional procedure was shortened with S-3DE display as compared with standard 3D display (17.3+/-3.1 min vs 23.0+/-3.9 min, P<0.05). Stereoscopic three-dimensional echocardiography could improve the visualization of three-dimensional echocardiography, facilitate the identification of the adjacent structures, decrease the time required for interventional manipulation. It may be a feasible, safe, and efficient tool for guiding transcatheter septal occlusion or the surgical interventions.

Surface-initiated activators generated by electron transfer for atom transfer radical polymerization in detection of DNA point mutation.

Amplification-by-Polymerization reportedly offers a sensitive and detector-free approach for DNA detection. However, the requirement for an oxygen-free environment when classic radical polymerization reactions are used in signal amplification significantly limits the mobility of this approach for point-of-need applications. We report here the employment of a purge-free controlled/"living" polymerization reaction, activators generated by electron transfer for atom transfer radical polymerization (AGET ATRP), to achieve signal amplification upon DNA hybridization. Its aptitude in simplifying assay procedure and shortening assay turn-around has been demonstrated in this report, which substantiates the feasibility of using Amplification-by-Polymerization for high throughput or portable screening of genetic mutations. In addition, employment of water-soluble ascorbic acid as the reducing agent has overcome the hurdles encountered by heterogeneous AGET ATRP reactions. Optimization of AGET ATRP in the presence of oligonucleotides has been conducted where tris[(2-pyridyl)methyl]amine (TPMA) was selected as the catalyst ligand for its mild reaction rate. Effective polymer growth has been achieved when the concentration of the Cu(II) catalyst was controlled at 20 mM and ascorbic acid at 18 mM. The propagation and termination reaction constants have been derived, purporting the speculated controlled growth kinetics during polymer grafting. A linear relationship between the grafted polymer film thickness and the amount of captured DNA target sequences has been established, which provides the quantification basis during DNA detection. Detection of DNA sequences with single-point mutations has been successful regardless of the mutation site.

Positive association between the PDLIM5 gene and bipolar disorder in the Chinese Han population.

BACKGROUND: Bipolar disorder is a widespread and severe brain disorder that is strongly affected by genetic factors. The PDZ and LIM domain 5 (PDLIM5) gene encodes a protein as an Enigma homologue LIM domain protein, which has been widely reported as being expressed in various brain regions. The analysis of DNA microarrays in the frontal lobes of patients with bipolar disorder has indicated changes in the expression level of PDLIM5, and subsequent studies have suggested that PDLIM5 might play a role in susceptibility to bipolar disorder. We sought to examine the association between PDLIM5 and bipolar disorder. METHODS: We recruited 502 patients with bipolar disorder and 507 controls from Anhui Province, China. We conducted a case-control study of 4 single-nucleotide polymorphisms (SNPs) of PDLIM5 that have been reported to be significantly associated with bipolar disorder in the Japanese and Chinese population: rs10008257, rs2433320, rs2433322 and rs2438146. RESULTS: We found that rs2433322 showed significantly different frequencies between patients and controls (p = 0.002). Three of the SNPs, rs10008257, rs2433320 and rs2438146, showed no statistical association with bipolar disorder; however, haplotypes constructed from 3 SNPs, rs2433320, rs2433322 and rs2438146, were significantly associated with bipolar disorder (global p = 0.004 after Bonferroni correction). LIMITATIONS: Our genetic association study only offered evidence for susceptibility of PDLIM5 to bipolar disorder, but the positive SNP rs2433322 could not indicate a direct cause of this complicated brain disorder. In addition, the 4 tagged SNPs that we selected could not cover the whole region of PDLIM5, thus additional reproducible studies of more SNPS in large non-Asian populations are needed. CONCLUSION: Our results suggest that PDLIM5 might play a role in susceptibility to bipolar disorder among the Chinese Han population.

Phenylboronic acid immunoaffinity reactor coupled with flow injection chemiluminescence for determination of alpha-fetoprotein.

A reusable and sensitive immunoassay based on phenylboronic acid immunoaffinity reactor in combination with flow injection chemiluminescence (CL) for determination of glycoprotein was described. The reactor was fabricated by immobilizing 3-aminophenylboronic acid (APBA) on glass microbeads with gamma-glycidoxypropyltrimethoxysilane (GPMS) as linkage. The alpha-fetoprotein (AFP) could be easily immobilized on the APBA coated beads through sugar-boronic interaction. After an off-line incubation, the mixture of the analyte AFP with horseradish peroxidase-labeled AFP antibody (HRP-anti-AFP) was injected into the reactor. This led the trapping of free HRP-anti-AFP by the surface coated AFP on glass beads. The trapped HRP-anti-AFP was detected by chemiluminescence due to its sensitizing effect on the reaction of luminol and hydrogen peroxide. Under optimal conditions, the chemiluminescent signal was proportional to AFP concentration in the range of 10-10 0 ng m L(-1). The whole assay process including regeneration of the reactor could be completed within 31 min. The proposed system showed acceptable detection and fabrication reproducibility, and the results obtained with the present method were in acceptable agreement with those from parallel single-analyte test of practical clinical sera. The described method enabled a low-cost, time saving and was potential to detect the serum AFP level in clinical diagnosis.

Clinical features and mismatch repair genes analyses of Chinese suspected hereditary non-polyposis colorectal cancer: a cost-effective screening strategy proposal.

China has the largest numbers of hereditary non-polyposis colorectal cancer (HNPCC) patients based on its population of 1.4 billion. However, the clinical data and mismatch repair (MMR) gene analyses have been limited. Here we performed microsatellite instability (MSI) and immunohistochemistry (IHC) analyses on a series of patients with a high-risk for HNPCC: 61 patients with family histories fulfilling Amsterdam criteria II (ACII-HNPCC) or suspected HNPCC criteria (S-HNPCC), and 106 early onset colorectal cancer (CRC) patients. Sixty late-onset CRC patients were used as control. Methylation of the hMLH1 promoter was analyzed on tumors lacking hMLH1 expression. MMR germ-line mutations were screened on patients with tumors classified as MSI-H/L or negative for IHC. We identified 27 germ-line MMR variants in the 167 patients with a high-risk for HNPCC while only one germ-line mutation in hMSH6 was found in the late-onset CRC group. Of those, 23 were pathogenic mutations. The high incidence of gastric and hepatobiliary cancers coupled with the increasing number of small families in China reduces the sensitivity (43.5%, 30.4%) and positive predictive value (PPV) (45.5%, 17.9%) of the ACII- or S-HNPCC criteria. MSI or IHC testing are highly sensitive in detecting pathogenic mutations (sensitivities = 91.3% and 95.6%, respectively), but the PPVs are quite low (25.6% and 27.8%, respectively). Considering that all 12 tumors with pathogenic mutations in hMLH1 also showed promoter unmethylation, the sensitivity of IHC in conjunction with hMLH1 promoter methylation analysis is not reduced, but the PPV was increased from 27.8% to 61.1%, and the total cost was greatly reduced.

Quantitative assessment of the effect of angiotensinogen gene polymorphisms on the risk of coronary heart disease.

BACKGROUND: Angiotensinogen, a key protein in the renin-angiotensin system, plays an important role in cardiovascular hemostasis. Many studies have examined the association between polymorphisms in the angiotensinogen gene and risk of coronary heart disease (CHD), but the results have been inconsistent. METHODS AND RESULTS: We performed a meta-analysis of 43 associations studies on 2 angiotensinogen polymorphisms (M235T and T174M) and risk of CHD published before March 2007, including a total of 13,478 CHD cases and 17,024 controls. We also explored potential sources of heterogeneity. In a combined analysis, the summary per-allele odds ratio for CHD of the M235T polymorphism was 1.11 (95% confidence interval, 1.03 to 1.19). However, when the analyses were restricted to 4 larger studies (n >500 cases), the summary per-allele odds ratio was 0.99 (95% confidence interval, 0.94 to 1.04). Our analyses detected a possibility of publication bias with an overestimate of the true association by smaller studies. A meta-analysis of studies on the 174M variant showed no significant overall association with CHD, yielding a per-allele odds ratio of 1.07 (95% confidence interval, 0.93 to 1.22). CONCLUSIONS: This meta-analysis suggested an overall weak association between the M235T polymorphism and CHD risk. However, the association was not observed in several larger studies, suggesting a publication bias. Additional very large-scale studies are warranted to provide conclusive evidence on the effects of the angiotensinogen gene and other genes within the renin-angiotensin system on risk of CHD.

Assessment of atrial septal defect area changes during cardiac cycle by live three-dimensional echocardiography.

OBJECTIVES: To investigate the accuracy of measurement of the atrial septal defect (ASD)area and dynamic change by live three-dimensional echocardiography (L3DE). METHODS: L3DE was performed in patients with ASD using a three-dimensional workstation to obtain the en face view of the ASD and measure its area at the peak of P-wave, the peak of R-wave, the initial and the destination point of T-wave, and the period of P-T. Parameters derived from L3DE were compared with intraoperative measurements. RESULTS: The ASD area changed significantly during cardiac cycles (mean change 46.1%, p < 0.0001; range 15.2-72.5%), with the maximal area at endsystole and the minimal area at enddiastole. There was excellent correlation between L3DE and intraoperative measurements for the area of ASD at the peak of P-wave (r = 0.92). There were good correlations between the two methods during the other phases of cardiac cycle (r = 0.81-0.86). CONCLUSIONS: L3DE provides accurate and feasible measurements of the ASD area. Investigation of the dynamic changes during the cardiac cycle may lead to an improved understanding of the hemodynamics of ASD.