The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained.No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p < 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p < 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p < 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups.Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.
Musculoskeletal system gradually degenerates with aging, and a hypoxia environment at a high altitude may accelerate this process. However, the comprehensive effects of high-altitude environments on bones and muscles remain unclear. This study aims to compare the differences in bones and muscles at different altitudes, and to explore the mechanism and influencing factors of the high-altitude environment on the skeletal muscle system.This is a prospective, multicenter, cohort study, which will recruit a total of 4000 participants over 50 years from 12 research centers with different altitudes (50m~3500m). The study will consist of a baseline assessment and a 5-year follow-up. Participants will undergo assessments of demographic information, anthropomorphic measures, self-reported questionnaires, handgrip muscle strength assessment (HGS), short physical performance battery (SPPB), blood sample analysis, and imaging assessments (QCT and/or DXA, US) within a time frame of 3 days after inclusion. A 5-year follow-up will be conducted to evaluate the changes in muscle size, density, and fat infiltration in different muscles; the muscle function impairment; the decrease in BMD; and the osteoporotic fracture incidence. Statistical analyses will be used to compare the research results between different altitudes. Multiple linear, logistic regression and classification tree analyses will be conducted to calculate the effects of various factors (e.g., altitude, age, and physical activity) on the skeletal muscle system in a high-altitude environment. Finally, a provisional cut-off point for the diagnosis of sarcopenia in adults at different altitudes will be calculated.The study has been approved by the institutional research ethics committee of each study center (main center number: KHLL2021-KY056). Results will be disseminated through scientific conferences and peer-reviewed publications, as well as meetings with stakeholders.http://www.chictr.org.cn/index.aspx, identifier ChiCTR2100052153.
Measurement of biomarkers early after acute myocardial infarction (AMI) might provide a cost-effective and widely available tool to assess infarct severity, myocardial dysfunction, and clinical outcomes. We aimed to induce AMI in miniature pigs, measure the levels of serum biomarkers and global LV function dynamically and explore the release kinetics and optimal sampling time points of copeptin and its correlation with global LV function.We induced AMI in the experimental group using a closed-chest model. Left ventricular (LV) function was detected by dual-source computed tomography (DSCT) and serum copeptin was determined by ELISA.The serum copeptin levels were increased at 1 hour, peaked at 3 hours, gradually decreased after 6 hours, and returned to baseline 3 days after AMI. At 3 to 6 hours, the copeptin cutoff of 16.97 to 17.44 pmol/l had 100% sensitivity and 100% specificity (P ⩽ .001) for AMI. Serum copeptin levels at 3 hours and 3 days were negatively correlated with the 3-hours LVEF (P ⩽ .001), respectively.Serum copeptin levels change in time, and measurements at 3 to 6 hours after AMI had the highest predictive value.
Knowledge of CT characteristics of COVID-19 pneumonia might be helpful to the early diagnosis and treatment of patients, and to control the spread of infection.The chest CT images of the patient were collected to describe the CT manifestations and characteristics, and they were compared with the previous studies.Multiple patchy ground-glass opacities (GGOs) were seen in bilateral lung, mostly in subpleural areas. They progressed within 3 days, and nodular GGOs were also seen together with subpleural patchy GGOs.Our case of COVID-19 pneumonia showed multiple subpleural GGOs in bilateral lung, rapid progression, and it also accompanied nodular GGOs on chest CT. These findings were consistent with the previous reports, and they might be useful for early detection and evaluation of severity of COVID-19 pneumonia.
Tuberculous meningomyelitis is a relatively rare but serious type of nervous system tuberculosis. This disease is caused by invasion of the spinal cord or the spinal meninges tuberculosis. The early symptoms are not typical and lack specificity. It can cause early changes in the MRI. Analysis of the MRI manifestations combined with the clinical manifestations and cere- brospinal fluid examination can facilitate accurate diagnosis of the disease. Early treatment has a clear effect, we want to increase knowledge of the dis- ease by sharing this case in order to reduce clinical misdiagnosis and allow more patients to be treated in time.
BACKGROUND First-generation and second-generation dual-source computed tomography (DSCT) are useful for analyzing left ventricle (LV) structure and function. This pilot study aimed to investigate the feasibility and role of third-generation DSCT for the evaluation of dynamic changes in LV structural and functional characteristics in a Diannan small-ear pig model of acute myocardial infarction (AMI). MATERIAL AND METHODS The model of AMI was established by balloon occlusion of the distal third of the left anterior descending (LAD) coronary artery in 14 Diannan small-eared pigs. Third-generation DSCT was performed to observe dynamic changes in LV structure and function before and after AMI was induced, with a follow-up period of 30 days. RESULTS The mean structural measurements at baseline included interventricular septum thickness (8.50±0.90 mm), LV anterior wall thickness (8.40±1.30 mm), LV posterior wall thickness (7.80±1.20 mm), LV end-diastolic dimension (LVEDD) (45.00±4.90 mm), and LV end-systolic dimension (LVESD) (25.90±4.10 mm). The mean functional measurements at baseline included the LV end-diastolic volume (LVEDV) (74.62±13.54 ml), LV end-systolic volume (LVESV) (23.06±7.46 ml), LV ejection fraction (LVEF) (69.29±6.83%), LV mass (86.35±14.02 g), stroke volume (SV) (51.56±9.77 ml), and cardiac output (CO) (4.22±2.14 l/min). Trends of time-dependent changes were observed for LVESV, LVEF, SV, and CO, but not for LVEDV or LV mass. CONCLUSIONS Third-generation DSCT was validated as a tool for assessing dynamic changes in LV global function in a porcine model of AMI.
Cerebral ischemic stroke (CIS) is one of the common causes of death and disability worldwide. This study aims to investigate effect of miR-137 on endothelial progenitor cells and angiogenesis in CIS by targeting NR4A2 via the Notch pathway. Brain tissues were extracted from CIS and normal mice. Immunohistochemistry was used to determine positive rate of NR4A2 expression. Serum VEGF, Ang, HGF, and IκBα levels were determined by ELISA. RT-qPCR and Western blotting were used to determine expression of related factors. Endothelial progenitor cells in CIS mice were treated and grouped into blank, NC, miR-137 mimic, miR-137 inhibitor, siRNA-NR4A2, and miR-137 inhibitor + siRNA-NR4A2 groups, and cells in normal mice into normal group. Proliferation and apoptosis were determined by MTT and flow cytometry, respectively. NR4A2 protein expression was strongly positive in CIS mice, which showed higher serum levels of VEGF, Ang, and HGF but lower IκBα than normal mice. Compared with normal group, the rest groups (endothelial progenitor cells from CIS mice) showed decreased expressions of miR-137, Hes1, Hes5, and IκBα but elevated NR4A2, Notch, Jagged1, Hey-2, VEGF, Ang, and HGF, inhibited proliferation and enhanced apoptosis. Compared with blank and NC groups, the miR-137 mimic and siRNA-NR4A2 groups exhibited increased expression of miR-137, Hes1, Hes5, and IκBα, but decreased NR4A2, Notch, Jagged1, and Hey-2, with enhanced proliferation and attenuated apoptosis. The miR-137 inhibitor group reversed the conditions. miR-137 enhances the endothelial progenitor cell proliferation and angiogenesis in CIS mice by targeting NR4A2 through the Notch signaling pathway.
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