Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept: a quantitative analysis based on 4D label-free technique.

AIM: To identify different metabolites, proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy (PDR) and resistance to anti-vascular endothelial growth factor (VEGF) drugs, and to provide biomarkers for the diagnosis and treatment of PDR. METHODS: Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analyses based on 4D label-free technology. Statistically differentially expressed proteins (DEPs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representation and protein interactions were analyzed. RESULTS: A total of 12 samples were analyzed. The proteomics results showed that a total of 58 proteins were identified as DEPs, of which 47 proteins were up-regulated and 11 proteins were down-regulated. We found that C1q and tumor necrosis factor related protein 5 (C1QTNF5), Clusterin (CLU), tissue inhibitor of metal protease 1 (TIMP1) and signal regulatory protein alpha (SIRPα) can all be specifically regulated after aflibercept treatment. GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR. In addition, protein-protein interaction (PPI) network evaluation revealed that TIMP1 plays a central role in neural regulation. In addition, CD47/SIRPα may become a key target to resolve anti-VEGF drug resistance in PDR. CONCLUSION: Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR. Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept, among which C1QTNF5, CLU, TIMP1 and SIRPα may become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Abnormal Systemic and Ocular Responses to the Valsalva Manoeuvre in Primary Open-Angle Glaucoma: A Case for Autonomic Failure?

OBJECTIVE: This study aimed to examine the association of primary open-angle glaucoma (POAG) with autonomic dysfunction by assessing the differences in systemic and ocular responses to an autonomic provocation test, the Valsalva manoeuvre (VM), between POAG patients and normal subjects. METHODS: Forty POAG and forty control subjects were subjected to the VM. Systemic and ocular parameters were measured at baseline, phase 2, and phase 4 of the VM (VM2 and VM4), where VM2 and VM4 are sympathetic and parasympathetic nervous activation states, respectively. Heart rate variability was used to assess the autonomic nervous activity, among which the high-frequency component (HF) and the low-frequency (LF)/HF ratio were used as indices of parasympathetic and sympathetic activation, respectively. RESULTS: POAG patients demonstrated higher sympathetic activation (LF/HF ratio median: 2.17 vs. 1.53, P=0.000) than controls at baseline and exhibited attenuated sympathetic and parasympathetic responses (a smaller change in LF/HF and HF values) during the VM than controls. During VM, the intraocular pressure (IOP), mean blood pressure (MAP), mean ocular perfusion pressure (MOPP), and the Schlemm's canal area (SCAR) increased from baseline to VM2 and then decreased from VM2 to VM4 in both the POAG and control groups (all P<0.05). However, when we compared the changes above, the fluctuations in IOP, MAP, and MOPP were more pronounced in POAG than in controls (all P<0.05), while the changes in amplitudes of SCAR were smaller in POAG (P<0.05). Furthermore, from VM2 to VM4, the choroid thickness (ChT) in the POAG group was significantly decreased, while it was unchanged in normal subjects (P=0.258). A regression analysis showed a significant correlation of the baseline LF/HF with IOP change values (ΔIOP) from baseline to VM2 in POAG (R2=0.147, P=0.014). CONCLUSION: Patients with POAG showed more pronounced fluctuations in IOP, MAP, MOPP and ChT during the VM than controls. These reactions could be associated with autonomic dysfunction in POAG.

Three-dimensional echocardiographic assessment of left ventricular volume in different heart diseases using a fully automated quantification software.

BACKGROUND: HeartModel (HM) is a fully automated adaptive quantification software that can quickly quantify left heart volume and left ventricular function. This study used HM to quantify the left ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV) of patients with dilated cardiomyopathy (DCM), coronary artery heart disease with segmental wall motion abnormality, and hypertrophic cardiomyopathy (HCM) to determine whether there were differences in the feasibility, accuracy, and repeatability of measuring the LVEDV, LVESV, LV ejection fraction (LVEF) and left atrial end-systolic volume (LAESV) and to compare these measurements with those obtained with traditional two-dimensional (2D) and three-dimensional (3D) methods. AIM: To evaluate the application value of HM in quantifying left heart chamber volume and LVEF in clinical patients. METHODS: A total of 150 subjects who underwent 2D and 3D echocardiography were divided into 4 groups: (1) 42 patients with normal heart shape and function (control group, Group A); (2) 35 patients with DCM (Group B); (3) 41 patients with LV remodeling after acute myocardial infarction (Group C); and (4) 32 patients with HCM (Group D). The LVEDV, LVESV, LVEF and LAESV obtained by HM with (HM-RE) and without regional endocardial border editing (HM-NE) were compared with those measured by traditional 2D/3D echocardiographic methods to assess the correlation, consistency, and repeatability of all methods. RESULTS: (1) The parameters measured by HM were significantly different among the groups (P < 0.05 for all). Compared with Groups A, C, and D, Group B had higher LVEDV and LVESV (P < 0.05 for all) and lower LVEF (P < 0.05 for all); (2) HM-NE overestimated LVEDV, LVESV, and LAESV with wide biases and underestimated LVEF with a small bias; contour adjustment reduced the biases and limits of agreement (bias: LVEDV, 28.17 mL, LVESV, 14.92 mL, LAESV, 8.18 mL, LVEF, -0.04%). The correlations between HM-RE and advanced cardiac 3D quantification (3DQA) (r s = 0.91-0.95, P < 0.05 for all) were higher than those between HM-NE (r s = 0.85-0.93, P < 0.05 for all) and the traditional 2D methods. The correlations between HM-RE and 3DQA were good for Groups A, B, and C but remained weak for Group D (LVEDV and LVESV, r s = 0.48-0.54, P < 0.05 for all); and (3) The intraobserver and interobserver variability for the HM-RE measurements were low. CONCLUSION: HM can be used to quantify the LV volume and LVEF in patients with common heart diseases and sufficient image quality. HM with contour editing is highly reproducible and accurate and may be recommended for clinical practice.

Annular plane systolic excursion Z-scores in evaluation of heart systolic function of fetus with heart failure.

OBJECTIVE: To compare fetal tricuspid annular plane systolic excursion(TAPSE）Z-scores and mitral annular plane systolic excursion(MAPSE) Z-scores between fetuses with heart failure (HF) and normal fetuses, and to analysis the correlation between CVPS and annular plane systolic excursion(APSE) Z-score(sum of the TAPSE and MAPSE Z-score) in order to evaluate the ventricle systolic function and severity in fetuses with HF. METHODS: A total of 1012 normal fetuses and 24 fetuses with heart failure were involved. TAPSE and MAPSE were measured by free angle M-mode(FAM) echocardiography. Normal FAM-TAPSE and FAM-MAPSE Z-score models based on GA were constructed by performing a standard regression analysis followed by weighted regression of absolute residual values . Tei indexes were calculated in all fetuses with heart failure and all of them were divided into left heart failure (LHF)group and right heart failure（RHF)group by Tei index. Subsequently, FAM-MAPSE Z-scores were compared between the normal and LHF groups, FAM-TAPSE Z-scores were compared between the normal and RHF groups．FAM-APSE Z-scores (sum of the FAM-TAPSE and FAM-MAPSE Z-score) and the cardiovascular profile scores (CVPS) in 24 fetuses were calculated, the correlation was analyzed among them. RESULTS: The models used to calculate Z-score for FAM-TAPSE and FAM-MAPSE were constructed, and GA had significant correlation with them (r = 0.949, p < 0.001for all)．Compared with normal fetuses, the mean Z-scores of FAM-TAPSE and FAM-MAPSE were statistically significantly different in fetuses with HF．In the HF groups, all FAM-TAPSE and FAM-MAPSE Z-scores(22/22) were <-2. CVPS ranged from 3 to 8 (mean 5.25 out of 10) and correlated positively with FAM-APSE Z-score (r = 0.762). CONCLUSIONS: The FAM-TAPSE and FAM-MAPSE Z-scores declined in fetuses with HF and they can provide quantitative evidence in evaluation of heart systolic function, FAM-APSE Z-score correlated positively with CVPS. FAM-TAPSE, FAM-MAPSE and FAM-APSE Z-scores would be markers for assessing heart systolic function and severity in fetuses with HF.

Association Between Out-of-Hour Admission and Short- and Long-Term Mortality in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.

Objectives: Out-of-hour admission (on weekends, holidays, and weekday nights) has been associated with higher mortality in patients with acute myocardial infarction (AMI). We conducted a meta-analysis to verify the association between out-of-hour admission and mortality (both short- and long-term) in AMI patients. Design: This Systematic review and meta-analysis of cohort studies. Data Sources: PubMed and EMBASE were searched from inception to 27 May 2021. Eligibility Criteria for Selected Studies: Studies of any design examined the potential association between out-of-hour admission and mortality in AMI. Data Extraction and Synthesis: In total, 2 investigators extracted the data and evaluated the risk of bias. Analysis was conducted using a random-effects model. The results are shown as odds ratios [ORs] with 95% confidence intervals (CIs). I 2 value was used to estimate heterogeneity. Grading of Recommendations Assessment, Development, and Evaluation was used to assess the certainty of the evidence. Results: The final analysis included 45 articles and 15,346,544 patients. Short-term mortality (defined as either in-hospital or 30-day mortality) was reported in 42 articles (15,340,220 patients). Out-of-hour admission was associated with higher short-term mortality (OR 1.04; 95%CI 1.02-1.05; I 2 = 69.2%) but there was a significant statistical indication for publication bias (modified Macaskill's test P < 0.001). One-year mortality was reported in 10 articles (1,386,837 patients). Out-of-hour admission was also associated with significantly increased long-term mortality (OR 1.03; 95%CI 1.01-1.04; I 2 = 66.6%), with no statistical indication of publication bias (p = 0.207). In the exploratory subgroup analysis, the intervention effect for short-term mortality was pronounced among patients in different regions (p = 0.04 for interaction) and socio-economic levels (p = 0.007 for interaction) and long-term mortality was pronounced among patients with different type of AMI (p = 0.0008 for interaction) or on different types of out-to-hour admission (p = 0.006 for interaction). Conclusion: Out-of-hour admission may be associated with an increased risk of both short- and long-term mortality in AMI patients. Trial Registration: PROSPERO (CRD42020182364).

[Identification of active components in Xuefu Zhuyu Decoction based on targets of blood-activating function].

As a classic prescription for promoting blood circulation to remove blood stasis, Xuefu Zhuyu Decoction(XFZYD) is widely used in clinical practice and has notable curative effect. Based on the key targets of activating blood circulation, this study identified the active components of XFZYD to reveal the material basis. The components of XFZYD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The molecular docking models were built for the blood-activating targets obtained from the previous study with the components of XFZYD. The top five active components with measurability for each target were selected as the potential blood-activating components in the prescription. The efficacy of the prescription can embody key pharmacological and high-content components. In this study, anti-platelet aggregation activity was used to characterize the effect of activating blood, and the in vivo experiments were conducted to verify the accuracy of the active components. A total of 210 chemical components of XFZYD were screened out from TCMSP and docked with the key targets with the function of activating blood. Ligustrazine, acteoside, naringin, etc. were selected as the potential active components for activating blood in XFZYD. The anti-platelet aggregation activity of the combination of Chuanxiong Rhizoma, Rehmanniae Radix, Aurantii Fructus, Glycyrrhizae Radix et Rhizoma, and Carthami Flos was 9.82%±5.11%. Compared with that in the control group, the platelet aggregation induced by adenosine diphosphate(ADP) was significantly inhibited in the test group(P<0.01), which verified the accuracy of the active components. This study can guide the research on the material basis of XFZYD and provide insights into the development and utilization of the classical prescription.

Reference ranges and Z-scores of atrioventricular and ventriculoatrial time intervals in normal fetuses.

OBJECTIVE: To establish a reference range and compare differences among three methods, and then to construct Z-score reference ranges in normal fetuses from the three methods to provide an extra tool for fetal conduction time assessment. METHODS: A total of 227 echocardiographic examinations were finally included. Fetal atrioventricular (AV) time and ventriculoatrial (VA) time intervals were measured by three methods: superior vena cava/ascending aorta (SVC/AAO), pulmonary artery/pulmonary vein (PA/PV) and tissue Doppler imaging (TDI). Regression analysis of the mean and standard deviation was performed to establish Z-scores. RESULTS: With the three methods, positive correlations of intervals with gestational age (GA) and fetal heart rate (FHA) were observed, while intervals were negatively correlated with fetal heart rate (FHR). Correlations between VA/AV and GA, FHA and FHR were weak. The general trend of all intervals was towards an increase. In AV intervals, PA/PV revealed the longest mean AV time interval and SVC/AAO showed the shortest interval. In addition, PA/PV revealed the shortest VA interval. CONCLUSION: This study presents not only the reference range of AV and VA intervals with the three methods but also the Z-score reference ranges for these indices against GA and FHA in normal fetuses. Each method has a different reference range, and appropriate application can facilitate diagnosis and treatment.

Quality of life in adult intermittent exotropia and the risk factors.

AIM: To study the quality of life of adult patients with intermittent exotropia (IXT) in China and analyze the factors affecting the quality of life in IXT patients. METHODS: Totally 109 cases of normal eye (control group), 77 cases of IXT (IXT group) and 115 cases of strabismus control group (except IXT) were collected. The quality of life of the patients was assessed by Chinese version of adult strabismus patient's quality of life scale (CAS-20). The differences of general characteristics, visual function and quality of life were analyzed, and the effects of individual factors and visual function on quality of life of patients with IXT were analyzed. RESULTS: The IXT group had a high proportion of patients with family history, low proportion of patients with amblyopia compared with strabismus control group. The proportion with normal near and far stereopsis of IXT group were lower than that of normal control group. The best corrected visual acuity of IXT group was higher than that of strabismus control group, but lower than the control group. In addition, the median strabismus degree in IXT group was higher than that in other strabismus control group. The median psychosocial scores and median visual function scores of the IXT group was lower than that of the normal control group, but not different from strabismus control group. Occupation status, course of disease, far stereopsis and near stereopsis significantly affected the quality of life in IXT patients. CONCLUSION: Adult IXT patients in China have a certain proportion of family history and lower quality of life, The main factors affecting the quality of life of IXT patients is stereopsis, course of disease and occupation status.

Isolated pulmonary valve endocarditis with rapid progression: a case report and literature review.

BACKGROUND: Isolated pulmonary valve endocarditis (IPE) is rare, accounting for 1.5-2% of all cases of infective endocarditis. Herein, we describe a case of isolated pulmonary valve endocarditis with rapid progression in a 28-year-old male. Unlike most patients reported previously who were cured with only anti-infective therapy, without surgery at an early stage, multiple complications occurred in this patient in less than 2 weeks. CASE PRESENTATION: The patient was diagnosed with pulmonary valve endocarditis with blood cultures showing Staphylococcus aureus and echocardiography revealing 2 masses (measuring 14*13 mm、11*16 mm in size). Only 12 days later, acute massive pulmonary embolism occurred. Then, repeated echocardiography revealed multiple masses attached to the pulmonary valve with severe pulmonary insufficiency and the possibility of pulmonary valve destruction. Finally, pulmonary valve replacement, vegetation removal, and right pulmonary thromboendarterectomy together with resection of the middle and lower lobes of the right lung were performed. CONCLUSIONS: The role of surgery at an early stage might need to be reconsidered, and it may be viable to combine medical and surgical approaches.

Reliability of Sonography-based Volume Computer Aided Diagnosis in the Normal Fetal Heart.

OBJECTIVES: To explore the inter- and intra-observer reliability of Sonography-based Volume Computer Aided Diagnosis (SonoVCAD) in the display of 8 diagnostic planes of fetal echocardiography and to evaluate its efficiency. METHODS: Three-dimensional volume data sets of the 56 normal singleton fetuses were acquired from a 4-chamber view by using a volume probe. After processing the data sets by using SonoVCAD, 8 cardiac diagnostic planes were displayed automatically. Three doctors with different experiences of performing fetal echocardiography evaluated each diagnostic plane and the success rates of 8 diagnostic planes were calculated. Inter-observer and intra-observer reliabilities were estimated by Cohen's kappa statistics. RESULTS: A total of 276 volume data sets acquired from the 56 normal fetuses were used for SonoVCAD analysis and display. The success rate of each diagnostic section was more than 90%, ranging from 90.6% to 99.6%. Among 276 volumes, 81.5% (225/276) of volumes were able to generate all 8 diagnostic views successfully. Moderate to substantial agreement (kappa, 0.509-0.794) was found between 2 less experienced operators. Moderate to near-perfect agreement (kappa, 0.439-0.933) was found between an expert and 2 less experienced sonographers. Intra-observer reliability was substantial to near-perfect (kappa, 0.602-0.903). The efficiency of SonoVCAD was assessed. The expert spent less time than 2 less experienced examiners (P < 0.001) but no significant difference was found between 2 less experienced examiners (P = 0.176). Besides, SonoVCAD consumed significantly less time than 2-dimensional ultrasound (P < 0.001). CONCLUSIONS: SonoVCAD can significantly improve the success rates of 8 diagnostic planes in fetal echocardiography with low operator dependency, good reproducibility and high efficiency.

Evaluation of carotid atherosclerosis and related risk factors using ultrasonic B-Flow technology in elderly patients.

OBJECTIVE: This study was performed to identify the risk factors for carotid atherosclerotic plaque formation using B-Flow ultrasound. METHODS: In total, 120 patients who underwent bilateral carotid ultrasound examination were enrolled in this cross-sectional study. The intima-media thickness was measured, and the risk factors for carotid atheromatous plaque formation were investigated. RESULTS: Age, sex, medical history of hypertension, coronary heart disease, and diabetes were risk factors for carotid atheromatous plaque formation. Multivariate logistic regression analysis revealed that the main risk factors for carotid atheromatous plaque formation were male sex, advanced age, a high hemoglobin concentration, a high red cell distribution width, and a high low-density lipoprotein cholesterol concentration. CONCLUSION: The risk factors for carotid atheromatous plaque formation were basically the same as those for stroke. Early ultrasound examination of the carotid artery enables the identification of risk factors associated with stroke.

Stimulated emission assisted time-gated detection of a solid-state spin.

The nitrogen vacancy (NV) center in diamond is studied widely for magnetic field and temperature sensing at the nanoscale. Usually, the fluorescence is recorded to estimate the spin state of the NV center. Here we applied a time-gating technique to improve the contrast of the spin-dependent fluorescence. A NIR pulsed laser pumped the stimulated emission of the NV center and depleted the spontaneous emission that was excited by a green laser. We changed the relative delay between the NIR laser and the green laser. Then the spontaneous emission of the NV center in varied time windows was extracted by comparing the fluorescence intensities with and without the NIR laser. The results showed that the spin-dependent fluorescence contrast could be improved by approximately 1.8 times by applying the time gating. The background of the environment was eliminated due to temporal filtering. This work demonstrates that the stimulated emission assisted time-gating technique can be used to improve the performance of an NV center sensor in a noisy environment.

A rare case report: tricuspid valve prolapse due to spontaneous chordae rupture in a congenitally corrected transposition of the great arteries patient.

BACKGROUND: Congenitally corrected transposition of great arteries (CCTGA) is caused by atrioventricular and ventriculoarterial discordance. Cases of CCTGA with spontaneous chordae rupture of tricuspid valve have not been reported before. CASE PRESENTATION: Here we diagnosed a 38-year-old man, who was found CCTGA 14 years ago, as spontaneous chordae rupture by real-time three dimentional transesophageal echocardiography (RT-3D-TEE). The present case is the first report to describe a CCTGA patient combine with spontaneous chordae rupture in tricuspid valve. After tricuspid valve replacement, the patient was uneventful after 6 years' follow-up. CONCLUSION: We reported a rare case with spontaneous chordae rupture of tricuspid valve in a CCTGA patient and explored its etiology here. RT-3D-TEE is an important supplement to 2-dimentional transthoracic echocardiography and can provide more accurate detections in tricuspid valve diseases in CCTGA.

Prevalence of heterophoria in a population of school children in central China: the Anyang Childhood Eye Study.

AIM: To investigate the prevalence of heterophoria and the relationship between heterophoria and refractive error in a school-based study conducted in central China. METHODS: A total of 2363 7th-grade children were recruited into the cross-sectional school-based Anyang Childhood Eye Study (ACES) by cluster sampling method. Heterophoria was examined using alternate cover and cover-uncover testing. The Maddox rod and prism test were conducted at 33 cm and 6 m distance fixation. Uncorrected viual acuity (UCVA) and best-corrected viual acuity (BCVA) were recorded as logarithm of the minimum angle of resolution (logMAR) with cycloplegic autorefraction by administrating of Mydrin-P and 1.0% cyclopentolate. Hyperopia was defined as the spherical equivalent (SE) refraction of +0.50 D or greater, and higher hyperopia was defined as +2.00 D or greater. Emmetropia was defined as the SE refraction in the range of -0.49 to +0.49 D, and myopia was in the SE refraction range from -0.50 D to less. RESULTS: Totally 2260 students in grade 7 were examined. Response rate among eligible children was 95.64%. Totally 486 children, 22.66% of the population, were diagnosed with heterophoria in which 479 were diagnosed with exophoria at near distance, and 6 with esophoria. Totally 89 (4.15%) children were diagnosed with heterophoria in which 82 had exophoria, and 7 had esophoria at far distance. Exophoria was common at near fixation (22.33%). Myopia was examined to be related to exophoria at near distance (OR 3.03, 95%CI 2.33-3.95) and far distance fixation (OR 1.90, 95%CI 1.09-3.32). CONCLUSION: Exophoria is a predominant heterophoria for 7th-grade junior school in central China. Significant associations are discovered between heterophoria and refractive error. Hyperopia is associated with esophoria, and myopia is associated with exophoria.

Retinal vascular diameter changes assessed with a computer-assisted software after strabismus surgery.

AIM: To quantitatively investigate the retinal vascular diameter changes, analyzing the early and long-term effects on the retinal circulation, with 6-month follow-up. METHODS: Patients underwent horizontal strabismus surgery were enrolled prospectively. Retinal vessel diameters on color fundus photographs were assessed before and 1, 7d, 6mo after surgery, using a computer-assisted quantitative assessment software. To evaluate the retinal vascular caliber changes, retinal vascular diameters were calculated by means of the Parr-Hubbard formula as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). The arteriovenous ratio (AVR) was calculated as CRAE divided by CRVE. RESULTS: A total of 154 eyes of 104 consecutive patients were included. Compared with the data before surgery (121.55±24.67), the mean CRAE (131.18±28.29) significantly increased 1d after surgery (P=0.003), but went back to baseline level at 7d (118.89±30.35, P=0.15), and 6mo (123.22±15.32, P=0.60), so did the AVR (P<0.001, P=0.08, P=0.07). As for the mean CRVE, there was no significant difference between those four time points (172.43±33.25, 175.57±36.98, 174.03±40.18, 174.86±20.46, P=1.00). CONCLUSION: Strabismus surgery on both lateral and media rectus muscles, or single media rectus muscle may increase retinal blood flow during the early postoperative period, but would return to normal later. The number of transected anterior ciliary arteries rather might be the main cause of retinal hemodynamic changes early after strabismus surgery.

Novel foetal echocardiographic image processing software (5D Heart) improves the display of key diagnostic elements in foetal echocardiography.

BACKGROUND: To evaluate the clinical value of foetal intelligent navigation echocardiography (5D Heart) for the display of key diagnostic elements in basic sections. METHODS: 3D volume datasets of 182 normal singleton foetuses were acquired with a four chamber view by using a volume probe. After processing the datasets by using 5D Heart, eight cardiac diagnostic planes were demonstrated, and the image qualities of the key diagnostic elements were graded by 3 doctors with different experiences in performing foetal echocardiography. RESULTS: A total of 231 volume datasets acquired from the 182 normal foetuses were used for 5D Heart analysis and display. The success rate of 8 standard diagnostic views was 88.2%, and the success rate of each diagnostic view was 55.8-99.2% and 70.7-99.0% for the random four chamber view as the initial section and for the apical four chamber view as the initial section, respectively. The success rate of each diagnostic element in the 8 diagnostic sections obtained by 5D Heart was 58.9%~ 100%. Excellent agreement was found between experienced sonographers and less-experienced sonographers (kappa> 0.769). Inter- and intra-observer agreement were substantial to near-perfect, kappa values ranging from 0.612 to 1.000 (Cohen's kappa). CONCLUSIONS: 5D Heart can significantly improve the image quality of key diagnostic elements in foetal echocardiography with low operator dependency and good reproducibility.

Screening of Biomarkers Related to Ovarian Maturation and Spawning in Blunt Snout Bream (Megalobrama amblycephala) Based on Metabolomics and Transcriptomics.

In fish breeding practices, gamete maturity of females is vital to reproductive success. For some species, it is possible to estimate the female maturation status based on abdomen observation, but quite difficult for some species which mature at big size. To screen out the potential biomarker in fish blood relating to female maturation, we employed the approach integrating the UPLC-MS/MS and RNA-seq techniques to investigate the metabolites and genes reflecting the sexual maturation and spawning of female blunt snout bream Megalobrama amblycephala. The study included four groups, 1-year-old immature female individuals, 2-year-old immature female individuals, 2-year-old sexually mature female individuals, and 2-year-old sexually mature female individuals after 24 h of successful spawning. The upregulated metabolites in mature females were involved in "steroid hormone biosynthesis," "metabolic pathways," "glycerophospholipid metabolism," etc. compared with those of immature individuals. As the key intermediate of steroid hormone biosynthesis, 17α-hydroxypregnenolone exhibited the highest level in 2-year-old mature females than in the immature females. Meanwhile, the metabolites (i.e., dodecanoic acid and myristic acid) participating in fatty acid synthesis exhibited much lower levels in the females after spawning than those before spawning. In addition to the metabolites, the genes involved in ovarian steroidogenesis were significantly upregulated in the 2-year-old immature females compared to the 1-year-old immature females, indicating that the ovarian steroidogenesis plays important roles in ovarian development of M. amblycephala at the early stages. The significant upregulation of genes (i.e., itpr1, camk2, and mekk2) involved in the "GnRH signaling pathway" was observed in the mature females compared with the immature females, which indicated that the estrogen levels increased after female maturation in M. amblycephala. Moreover, many genes (e.g., gck, creb1, tf2-9, ryr2, asgr1, and creb1) regulating insulin secretion and thyroid hormone synthesis were significantly downregulated after female spawning. The dynamics of gene expression and metabolites observed in this study provide novel cues for guiding fish practical artificial reproduction.

Z-scores of early diastolic blood flow widths of mitral and tricuspid valves in normal fetuses and fetuses with dilated coronary sinus.

Objectives: To establish Z-score models for early diastolic blood flow widths of mitral and tricuspid valves in normal fetuses and compare Z-scores and other blood flow dynamic parameters between normal fetuses and fetuses with dilated coronary sinus (CS). This study seeks to assess whether dilated CS affects cardiac structure or hemodynamics.Methods: One hundred twenty-nine normal fetuses (Group I) and 15 fetuses with dilated CS connected to persistent left superior vena cava (PLSVC) (Group II) were included in this study. Noncardiac biometrical parameters, including gestation age (GA), biparietal diameter (BPD), femoral length (FL), and heart area (HA), were obtained. Hemodynamic parameters, such as the early diastolic blood flow widths of mitral and tricuspid valves (MV-CDFI-Width, TV-CDFI-Width), velocity and time integral of blood flow (VTI), peak early and late diastolic velocity of mitral and tricuspid valves [peak early diastolic velocity of the mitral valve (MVE), peak late diastolic velocity of the mitral valve (MVA), peak early diastolic velocity of the tricuspid valve (TVE), peak late diastolic velocity of the tricuspid valve (TVA)], were measured.Results: Z-score models for MV-CDFI-Width and TV-CDFI-Width against noncardiac biometrical parameters were best described by linear regression analysis. The mean equations of MV-CDFI-Width against noncardiac biometrical parameters were 0.066 + (0.025 × GA), 0.169 + (0.084 × BPD), 0.213 + (0.106 × FL) and 0.533 + (0.028 × HA). The SD for MV-CDFI-Width against FL was estimated based on values from the following equation: -0.006 + (0.02 × FL). Other SDs were constants estimated as the standard deviations of the unscaled residuals. Z-scores and other blood flow dynamic parameters exhibited no statistically significant differences between Group I and Group II.Conclusions: This study demonstrated that dilated CS did not affect fetal hemodynamics of the mitral or tricuspid valves or cardiac structures. We also suggested that the causes of diminutive left heart or coarctation of the aorta might not be associated with dilated CS in fetuses with PLSVC.

Is Fetal Intelligent Navigation Echocardiography Helpful in Screening for d-Transposition of the Great Arteries?

OBJECTIVES: To evaluate the performance of fetal intelligent navigation echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volumes in generating 3 specific abnormal cardiac views (left ventricular outflow tract, right ventricular outflow tract, and 3-vessel and trachea) used to screen for d-transposition of the great arteries (d-TGA). METHODS: In this prospective study, 1 or more STIC volumes were obtained from the 4-chamber view in 34 second- and third-trimester fetuses with d-TGA. Each appropriate STIC volume was evaluated by STICLoop (Samsung Medison, Seoul, Korea) before applying the FINE method. One optimal volume per fetus was selected by observers. The visualization rates of the 3 specific abnormal cardiac views of d-TGA and their diagnostic elements were calculated, and the reliability between 2 observers was verified by the intraclass correlation coefficient. RESULTS: Fetal intelligent navigation echocardiography applied to STIC volume data sets of fetuses with d-TGA successfully generated the 3 specific abnormal cardiac views in the following manner for 2 observers: 75.0% (n = 21) for the left ventricular outflow tract, 89.2% (n = 25) for the right ventricular outflow tract, and 85.7% (n = 24) for the 3-vessel and trachea view. Twenty-four (85.7%) of the STIC volume data sets showed 2 or 3 of the abnormal cardiac views. The interobserver intraclass correlation coefficients between the 2 observers ranged from 0.842 to 1.000 (95% confidence interval), indicating almost perfect reliability for the 2 observers. CONCLUSIONS: In cases of d-TGA, the FINE method has a high success rate in generating 3 specific abnormal cardiac views and therefore can be performed to screen for this congenital defect.