Diastolic dysfunction assessed by cardiac magnetic resonance imaging tissue tracking on normal-thickness wall segments in hypertrophic cardiomyopathy.

OBJECTIVES: Myocardial strain is reported to be a sensitive indicator of myocardial mechanical changes in patients with hypertrophic cardiomyopathy (HCM). The changes in the mechanics of the myocardium of normal wall thickness (< 12 mm) have yet to be well studied. This study aimed to evaluate the function of myocardial segments of normal thickness in patients with HCM. METHODS: Sixty-three patients with HCM and 30 controls were retrospectively enrolled in this retrospective study. Cine imaging, native and post-contrast T1 maps, T2 maps, and late gadolinium enhancement were performed. In addition, regional myocardial strain was assessed by cardiac magnetic resonance-tissue tracking. Strain parameters were compared between the controls and HCM patients with segments of the myocardium of normal thickness. Subgroup analysis was conducted in obstructive and non-obstructive HCM. Lastly, p < 0.05 was considered statistically significant. RESULTS: In normal-thickness myocardial segments of HCM (n = 716), diastolic peak strain rates (PSRs) were significantly lower than in the control group (n = 480) (radial, - 2.43 [- 3.36, - 1.78] vs. - 2.67 [- 3.58, - 1.96], p = 0.002; circumferential, 1.28 [1.01,1.60] vs. 1.39 [1.14, 1.78], p < 0.001; and longitudinal, 1.16 [0.75,1.51] vs. 1.28 [0.90, 1.71], p < 0.001). The normal-thickness segments showed no significant difference in systolic PSRs between HCM and the controls. In the subgroup analysis, significantly decreased diastolic PSRs were noted in both obstructive and non-obstructive HCM, compared with the controls (p < 0.05). CONCLUSIONS: Diastolic changes in myocardial mechanics were observed in normal-thickness segments of HCM, occurring before morphological remodeling and systolic dysfunction developed. This finding contributed to a better understanding of the mechanical pathophysiology of HCM with preserved left ventricular ejection fraction. It may potentially aid in predicting disease progression and risk stratification.

The major factor of left ventricular systolic dysfunction in patients with cardiac amyloidosis: Amyloid overload or microcirculation impairment?

Purpose: Amyloid overload and microcirculation impairment are both detrimental to left ventricular (LV) systolic function, while it is not clear which factor dominates LV functional remodeling in patients with cardiac amyloidosis (CA). The purpose of this study was to investigate the major factor of LV systolic dysfunction using cardiac magnetic resonance imaging. Materials and methods: Forty CA patients and 20 healthy controls were included in this study. The CA group was divided into two subgroups by the left ventricular ejection fraction (LVEF): patients with reduced LVEF (LVEF < 50%, rLVEF), and patients with preserved LVEF (LVEF ≥ 50%, pLVEF). The scanning sequences included cine, native and post-contrast T1 mapping, rest first-pass perfusion and late gadolinium enhancement. Perfusion and mapping parameters were compared among the three groups. Correlation analysis was performed to evaluate the relationship between LVEF and mapping parameters, as well as the relationship between LVEF and perfusion parameters. Results: Remarkably higher native T1 value was observed in the rLVEF patients than the pLVEF patients (1442.2 ± 85.8 ms vs. 1407.0 ± 93.9 ms, adjusted p = 0.001). The pLVEF patients showed significantly lower slope dividing baseline signal intensity (slope%BL; rLVEF vs. pLVEF, 55.1 ± 31.0 vs. 46.2 ± 22.3, adjusted p = 0.001) and a lower maximal signal intensity subtracting baseline signal intensity (MaxSI-BL; rLVEF vs. pLVEF, 43.5 ± 23.9 vs. 37.0 ± 18.6, adjusted p = 0.003) compared to the rLVEF patients. CA patients required more time to reach the maximal signal intensity than the controls did (all adjusted p < 0.01). There was no significant correlation between LVEF and first-pass perfusion parameters, while significant negative correlation was observed between LVEF and native T1 (r = -0.434, p = 0.005) in CA patients. Conclusion: Amyloid overload in the myocardial interstitium may be the major factor of LV systolic dysfunction in CA patients, other than microcirculation impairment.

The correlation of left atrial dysfunction and amyloid load in patients with immunoglobulin light-chain cardiac amyloidosis: a 3T cardiac magnetic resonance study.

OBJECTIVE: To investigate the left atrial (LA) changes in immunoglobulin light-chain cardiac amyloidosis (AL-CA) patients with different risk stratifications and to explore the correlation between LA function and the degree of amyloid load using cardiac magnetic resonance (CMR) imaging. METHODS: Forty-three AL-CA patients were retrospectively enrolled and were divided into low-to-moderate-risk group (n = 16, increased NT-proBNP or troponin I, or both normal) and high-risk group (n = 27, increased NT-proBNP and troponin I). 20 healthy individuals matched for age and gender were included. The function, myocardial deformation of left heart, and left ventricular (LV) tissue characterization among the three groups were compared. The correlation between LA function and LV tissue characterization was investigated. RESULTS: Compared with the controls, the AL-CA patients had a larger LA volume, lower left atrial emptying fraction (LAEF) and impaired left atrial strain (LAS). The high-risk group exhibited lower reservoir and booster function and increased LV extracellular volume (LV-ECV) than the low-to-moderate-risk group (p < 0.05). LV-ECV was significantly correlated with LAS and LAEF (all p < 0.05) but not LAEFconduit. The LAS and LAEF had a good diagnostic ability for risk stratification of AL-CA patients (area under the curve, 0.70 ~ 0.72). CONCLUSION: High-risk AL-CA patients showed more severe LA function impairment than low-to-moderate-risk AL-CA patients. LAS and LAEF were closely associated with LV-ECV in AL-CA patients, LAS and LAEF exhibited good capability to differentiate AL-CA patients of different risk stratifications. ADVANCES IN KNOWLEDGE: CMR-derived LAS and LAEF were correlated with amyloid load, allowing for differentiation of AL-CA patients at different risk stages.

Enhancing menaquinone-7 biosynthesis by adaptive evolution of Bacillus natto through chemical modulator.

Menaquinone-7 (MK-7) is a kind of vitamin K2 playing an important role in the treatment and prevention of cardiovascular disease, osteoporosis and arterial calcification. The purpose of this study is to establish an adaptive evolution strategy based on a chemical modulator to improve MK-7 biosynthesis in Bacillus natto. The inhibitor of 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase), glyphosate, was chosen as the chemical modulator to perform the experiments. The final strain ALE-25-40, which was obtained after 40 cycles in 25 mmol/L glyphosate, showed a maximal MK-7 titer of 62 mg/L and MK-7 productivity of 0.42 mg/(L h), representing 2.5 and 3 times the original strain, respectively. Moreover, ALE-25-40 generated fewer spores and showed a higher NADH and redox potential. Furthermore, the mechanism related to the improved performance of ALE-25-40 was investigated by comparative transcriptomics analysis. Genes related to the sporation formation were down-regulated. In addition, several genes related to NADH formation were also up-regulated. This strategy proposed here may provide a new and alternative directive for the industrial production of vitamin K2.

Cardiac involvement in patients 1 year after recovery from moderate and severe COVID-19 infections.

Background: Some patients suffered persistent cardiac symptoms after hospital discharge following COVID-19 infection, including chest tightness, chest pain, and palpitation. However, the cardiac involvement in these patients remains unknown. The purpose of this study was to investigate the effect of COVID-19 infection on the cardiovascular system after 1 year of recovery in patients hospitalized with persistent cardiac symptoms. Materials and methods: In this prospective observational study, a total of 32 patients who had COVID-19 (11 diagnosed as severe COVID-19 and 21 as moderate) with persistent cardiac symptoms after hospital discharge were enrolled. Contrast-enhanced cardiovascular magnetic resonance (CMR) imaging was performed on all patients. Comparisons were made with age- and sex-matched healthy controls (n = 13), and age-, sex- and risk factor-matched controls (n = 21). Further analysis was made between the severe and moderate COVID-19 cohorts. Results: The mean time interval between acute COVID-19 infection and CMR was 462 ± 18 days. Patients recovered from COVID-19 had reduced left ventricular ejection fraction (LVEF) (p = 0.003) and increased extracellular volumes (ECVs) (p = 0.023) compared with healthy controls. Focal late gadolinium enhancement (LGE) was found in 22 (68.8%) patients, mainly distributed linearly in the septal mid-wall or patchily in RV insertion point. The LGE extent in patients with severe COVID-19 was higher than that in patients with moderate COVID-19 (p = 0.009). Conclusion: This 1-year follow-up study revealed that patients with persistent cardiac symptoms, after recovering from COVID-19, had decreased cardiac function and increased ECV compared with healthy controls. Patients with COVID-19 predominately had a LGE pattern of septal mid-wall or RV insertion point. Patients with severe COVID-19 had greater LGE extent than patients with moderate COVID-19.

Discriminating malignant from benign testicular masses using machine-learning based radiomics signature of appearance diffusion coefficient maps: Comparing with conventional mean and minimum ADC values.

PURPOSE: To develop a machine-learning-based radiomics signature of ADC for discriminating between benign and malignant testicular masses and compare its classification performance with that of minimum and mean ADC. METHODS: A total of ninety-seven patients with 101 histopathologically confirmed testicular masses (70 malignancies, 31 benignities) were evaluated in this retrospective study. Eight hundred fifty-one radiomics features were extracted from the preoperative ADC map of each lesion. The mean and minimum ADC values are part of the radiomics features. Thirty lesions were randomly selected to estimate the reliability of the features. The redundant features were eliminated using univariate analysis (independent t test and Mann-Whitney U test, where appropriate) and Spearman's rank correlation. The least absolute shrinkage and selection operator (LASSO) algorithm was employed for feature selection and radiomics signature generation. The classification performance of the radiomics signature and minimum and mean ADC values were evaluated by receiver operating characteristic (ROC) curve analysis and compared by DeLong's test. RESULTS: The whole lesion-based mean ADC showed no difference between benign and malignant testicular masses (P = 0.070, training cohort; P = 0.418, validation cohort). Compared with the minimum ADC, the ADC-based radiomics signature yielded a higher area under the curve (AUC) in both the training (AUC: 0.904, 95% confidence interval [CI]: 0.832-0.975) and validation cohorts (AUC: 0.868, 95% CI: 0.728-1.00). CONCLUSIONS: Conventional mean ADC values are not always helpful in discriminating between testicular benignities and malignancies. The minimum ADC and radiomics signature might be better alternatives, with the radiomics signature performing better than the minimum ADC.

Transcriptomic analysis of gene expression of menaquinone-7 in Bacillus subtilis natto toward different oxygen supply.

Menaquinone-7 (MK-7) is an important kind of vitamin K2 which plays significant roles in the treatment of coagulation and osteoporosis, and prevention of cardiovascular disease. This work was purposed to study the differences of gene expression at different oxygen supply conditions in Bacillus natto. The differences of fermentation characteristics, gene expression related to MK-7 biosynthesis, spore and biofilm formation were analyzed. The yield of MK-7 increased by two fold under high oxygen supply condition of 200 rpm. Further transcriptome analysis indicated that most of the enzymes in MK-7 biosynthesis pathway were also up-regulated. Moreover, glycerol kinase, fructose-bisphosphate aldolase and phosphofructokinase in glycolysis pathway were all up-regulated indicating that high oxygen supply can increase the consumption of substrate glycerol. Meanwhile, menD, encoded the rate-limiting enzyme in the MK pathway, was obviously up-regulated by 3.49-fold while most of the enzymes related to spore formation were down regulated at 200 rpm. Besides, superoxide dismutase (SOD2), catalase (CAT), hydroperoxide reductase (AhpF) and DNA-binding protein MrgA in the antioxidant defense system were up-regulated, while superoxide dismutase (SOD1) and glutathione peroxidase (GSH-Px) were down-regulated. These results could contribute to a better understanding for the effect of oxygen on the MK-7 production in Bacillus natto, and further analyze the molecular regulation mechanism of MK-7 biosynthesis.

[Testicular microlithiasis influences seminal profile and testicular blood flow in infertile men].

OBJECTIVE: To investigate the testicular blood flow in patients with testicular microlithiasis (TM) and its correlation with the seminal profile in infertile men. METHODS: We selected 88 infertile men and examined them by testicular color Doppler and routine seminal tests. RESULTS: Testicular microlithiasis was found in 19 (19.3%) of the patients, classic testicular microlithiasis (CTM) in 7 (8.0%), and limited testicular microlithiasis (LTM) in 10 (11.3%). No significant differences were observed in the age of onset, bilateral testicular volume, resistance index (RI) of bilateral testicular arteries, semen amount and the rate of teratospermia. The bilateral testicular peak systolic velocity (PSV), sperm count and sperm motility were significantly lower in the CTM than in the LTM group (P < 0.05), but showed no statistically significant difference between the LTM and the non-calcification group. CONCLUSION: TM may be one of the causes of poor sperm function in infertile men.