Ultrasound­targeted microbubble destruction technology delivering ß­klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post­myocardial infarction.

Fibroblast growth factor (FGF)21 is a peptide hormone that improves mitochondrial function and energy metabolism, and the deficiency of its co­receptor ß­klotho (KLB) causes decreased FGF21 sensitivity. The present study examined whether the cardiac delivery of plasmids containing the KLB gene via ultrasound­targeted microbubble destruction (UTMD) enhances the efficacy of FGF21 against heart failure post­acute myocardial infarction (AMI). For this purpose, the levels of FGF21 in patients and rats with heart dysfunction post­infarction were determined using ELISA. Sprague­Dawley rats received the 3X UTMD­mediated delivery of KLB@cationic microbubbles (KLB@CMBs) 1 week following the induction of AMI. Echocardiography, histopathology and biochemical analysis were performed at 4 weeks following the induction of AMI. The results revealed that patients with heart failure post­infarction had higher serum FGF21 levels than the healthy controls. However, the downstream signal, KLB, but not α­klotho, was reduced in the heart tissues of rats with AMI. As was expected, treatment with FGF21 did not substantially attenuate heart remodeling post­infarction. It was found that decreased receptors KLB in the heart may result in the insensitivity to FGF21 treatment. In vivo, the UTMD technology­mediated delivery of KLB@CMBs to the heart significantly enhanced the effects of FGF21 administration on cardiac remodeling and mitochondrial dysfunction in the rats following infarction. The delivery of KLB to the heart by UTMD and the administration of FGF21 attenuated mitochondrial impairment and oxidative stress by activating nuclear factor erythroid 2­related factor 2 signals. On the whole, the present study demonstrates that the cardiac delivery of KLB significantly optimizes the cardioprotective effects of FGF21 therapy on adverse heart remodeling. UTMD appears a promising interdisciplinary approach with which to improve heart failure post­myocardial infarction.

Prediction of mechanical ventilation outcome by early abdominal-visceral-blood-flow-and-function score in critically ill patients after cardiopulmonary bypass in the ICU: A prospective observational study.

Background: Abdominal organs are important organs that sense and respond to ischemia and hypoxia, but there are few evaluation methods.We use ultrasonography to evaluate abdominal organ function and blood flow in patients with mechanical ventilation (MV) after cardiopulmonary bypass and to obtain a semiquantitative score for abdominal organ function and blood flow. Methods: Patients with cardiopulmonary bypass in the Critical Care Department of Peking Union Medical College Hospital in China from March to July 2021 were enrolled in this prospective observational study. The correlation of the abdominal-visceral-blood-flow-and-function score (AVBFS) with the duration of MV, number of days spent in the intensive care unit (ICU), acute physiology and chronic health evaluation II (APACHE-II), sequential organ failure assessment (SOFA), lactate, epinephrine, and norepinephrine use was analyzed, and the results were used to assess the predictive value of the receiver operating characteristic curve (ROC) regression analysis score for the duration of MV. Results: Of the 92 patients who underwent cardiopulmonary bypass, 41 were finally included. The AVBFS were significantly correlated with the duration of MV, number of days spent in the ICU, APACHE-II score, SOFA score, and norepinephrine use time. The AVBFS in a group of patients using ventilators ≥36 h were significantly higher than those obtained for a group of patients using ventilators <36 h (P <0.05). The evaluation results for the AVBFS at 0-12 h after ICU admission were as follows: area under the ROC curve (AUC)=0.876 (95% confidence interval [CI]: 0.767 to 0.984), cut-off value=2.5, specificity=0.842, and sensitivity=0.773. Conclusions: Abdominal visceral organ function and blood perfusion can be used to evaluate gastrointestinal function. It is related to early and late extubation after cardiac surgery.

A novel method for diaphragm-based electrode belt position of electrical impedance tomography by ultrasound.

BACKGROUND: This aim of study was to introduce a diaphragm-based EIT-belt placement method based on diaphragm position by ultrasound, and to evaluate the difference between diaphragm-based EIT-belt placement and conventional EIT-belt placement. METHOD: The diaphragm position (L0) determined by ultrasound was taken as zero reference level. The direction of headward is defined as positive, and toward feet is negative. For EIT data collection, the electrode belt was placed at 7 different levels, respectively (denoted as L-2 cm, L0, L2cm, L4cm, L6cm, L8cm, L10cm) at supine position in healthy volunteers. The diaphragm-based EIT-belt level (Lxcm) was defined where highest tidal impedance variation (TV) was achieved. Subsequently, EIT measurements were conducted at diaphragm-based EIT-belt levels and traditional EIT-belt level in 50 critically ill patients under mechanical ventilation. RESULT: The highest TV was achieved at L6cm and the smallest at L-2 cm., so the L6cm were taken as diaphragm-based EIT-belt level by ultrasound in 8 healthy volunteers. In 23 patients, the diaphragm-based EIT-belt plane agreed with the conventional planes (4th-6th ICS), which was defined as the Agreed group. Other patients were classified to the Disagreed group (above 4th ICS). The Disagreed group has a significantly higher BMI and lower global TV at the diaphragm-based EIT-belt plane compared to the Agreed group. CONCLUSIONS: The diaphragm-based EIT-belt position by ultrasound was feasible and resulted in different belt positions compared to the conventional position in > 50% of the examined subjects, especially in patients with higher BMI. Further study is required to validate the impact on EIT images with this novel method on clinical management.

Association between Dietary Choline Intake and Cardiovascular Diseases: National Health and Nutrition Examination Survey 2011-2016.

Choline is an essential nutrient for human body, but dietary choline is metabolized into the hazard metabolite for the cardiovascular system. Because of the conflicting results between dietary choline intake and cardiovascular disease (CVD) risk in previous studies, we aimed to investigate this in US adults. Non-pregnant participants and those aged >20 years from National Health and Nutrition Examination Survey 2011-2016, with CVD assessment and reliable dietary recall status, were included. The dietary choline intake was assessed as a mean value of two total dietary choline intakes, including dietary choline intake and supplemental choline intake, in 24-h dietary recall interviews. The association between dietary choline intake and the presence of CVD was examined using logistic regression. We enrolled 14,323 participants. The participants without CVD had substantially higher dietary choline intakes (318.4 mg/d vs. 297.2 mg/d) compared to those with CVD (p < 0.05). After multivariable adjustments, the highest quartile of dietary choline intake was associated with a lower CVD risk, OR 0.693, 95%CI [0.520, 0.923], when compared to the lowest quartile. Consistent results were also found for stroke. Subgroup analyses also supported these, especially in participants aged ≥60 years and in those with BMI < 30 kg/m2. We found that a higher dietary choline intake was associated with a lower CVD risk, especially the risk of stroke. Further clinical trials are needed in order to confirm this finding and to provide dietary suggestions for the appropriate amount of choline intake.

U-Shaped Relationship Between Cardiovascular Mortality and Serum Uric Acid May Be Attributed to Stroke- and Heart-Specific Mortality, Respectively, Among Hypertensive Patients: A Nationally Representative Cohort Study.

BACKGROUND Serum uric acid (UA) is involved in the development of hypertension. However, its impact on mortality in hypertension remains unclear. We aimed to assess the association of cardiovascular and all-cause mortality with UA in a hypertensive population. MATERIAL AND METHODS This study included 15 583 hypertensive patients from the NHANES study during 1999-2014. Weighted Cox regression analyses and cubic spline fitting were used to assess the relationship between UA and mortality risk. RESULTS Over a median follow-up of 7.4 years (116 351 person-years), a total of 3291 deaths occurred. Mortality was examined according to 5 predefined UA levels: £3.5, 3.5-5, 5-6, 6-7.5, and >7.5 mg/dL. In multivariable analysis with 5-6 mg/dL as a reference, the hazard ratios (95% confidence interval) of total mortality across the 5 groups were 1.40 (1.05-1.88), 1.08 (0.95-1.21), 1.00 (reference), 1.14 (1.02-1.29), and 1.74 (1.50-2.02), respectively. According to a restricted cubic spline, we noted a U-shaped relationship between UA and total mortality. The U-shaped relationship between UA and cardiovascular mortality remained in both females and males. The increased cardiovascular mortality in the lowest and highest UA groups was attributed to stroke and heart-specific mortality, respectively. However, serum UA was not significantly associated with cancer mortality. CONCLUSIONS Our findings showed a U-shaped relationship between serum UA levels and total and cardiovascular mortality in patients with hypertension. Furthermore, low UA was associated with stroke mortality, while higher UA was associated with heart-related mortality. Further research is needed to identify the potential mechanisms of UA in hypertension.

Heparanase Contributes To Trans-Endothelial Migration of Hepatocellular Carcinoma Cells.

The overall outcome of patients with hepatocellular carcinoma (HCC) is still very poor due to its high metastasis and recurrence rate. During metastasis, trans-endothelial migration (TEM) of HCC cells is a key step. Heparanase (HPSE) is an endo-beta-glucuronidase and exerts prometastatic properties for normal and tumor-derived cells. However, it is remains unclear that HPSE contributes to TEM of HCC cells. In this study, human umbilical vein endothelial cells-C (HUVEC-C) was used to simulate vascular endothelial cells (VECs), and the HCCLM3 cells with high HPSE expression were chosen and used for in vitro TEM assay and in vivo experiment. As results, we found that HCCLM3 cells showed higher TEM rate compared with other HCC cells. Downregulation or inhibition of HPSE activity resulted in suppression of TEM of HCC cells both in vitro and in vivo. Our findings suggest that HPSE contributes to TEM of HCC cells, which may be a new biological function of HPSE.