[Weight status related early changes in blood pressure, cardiac structure and function in 4-year-old children].

Objective: To explore the association between weight status and early changes in blood pressure, cardiac structure and function in children at 4 years of age. Methods: A cross-sectional study of the relationship between weight status and cardiovascular parameters was performed on the platform of "Shanghai Birth Cohort" in Shanghai Xinhua Hospital between 2017 and 2020. Height, weight, blood pressure and echocardiography were measured in 1 477 children at 4 years of age. According to body mass index (BMI), participants were classified into five groups: underweight, lean, normal weight, overweight and obese. Blood pressure, cardiac structure and function indexes were compared among different groups using one-way ANOVA. The associations between blood pressure, cardiac structure and function and weight status in children were analyzed by linear regression models. Multivariate logistic regression models were used to analyze whether weight status was an independent risk factor for elevated blood pressure or left ventricular hypertrophy (LVH) in children. Results: A total of 1 477 children including 772 boys and 705 girls were included in this study. There were 115 overweight and obese boys (14.9%) and 68 overweight and obese girls (9.6%). The majority of children had normal weight (916 cases, 62.0%), followed by underweight (303 cases, 20.5%), overweight (130 cases, 8.8%), lean (75 cases, 5.1%), and obese (53 cases, 3.6%). With the increase of BMI, systolic blood pressure, diastolic blood pressure, left ventricular mass index (LVMI), left ventricular posterior wall thickness in systole, left ventricular posterior wall thickness in diastole, left ventricular diameter in end-systole, left ventricular diameter in end-diastole, interventricular septum thickness in systole and left ventricular ejection fraction showed significantly positive trend, and the differences among the groups were significant (F=31.73, 6.59, 14.22, 4.96, 3.01, 31.50, 39.79, 5.91, 3.09, all P<0.05). Multiple linear regression showed that overweight and obese were all positively associated with systolic blood pressure (ß=5.2, 95%CI 3.6-6.8), LVMI (ß=1.9, 95%CI 0.8-3.1), left ventricular diameter in end-systole (ß=1.3, 95%CI 0.9-1.8), and left ventricular diameter in end-diastole (ß=1.6, 95%CI 1.0-2.2). In the Logistic regression model, compared with normal weight children, overweight (OR=2.37, 95%CI 1.37-4.41) and obese children (OR=10.90, 95%CI 4.47-26.60) both had significantly increased risk of elevated blood pressure. However, the risk of LVH did not significantly increased. Conclusions: Overweight and obesity in 4-year-old children are associated with increased blood pressure, increased left ventricle diameter and LVMI. Overweight and obesity are independent risk factors for elevated blood pressure in children at 4 years of age.

[Clinical and cardiac magnetic resonance features of apical hypertrophic cardiomyopathy patients complicating with left ventricular apical aneurysm].

Objective: To evaluate the clinical and cardiac magnetic resonance (CMR) features of apical hypertrophic cardiomyopathy (ApHCM) patients complicating with left ventricular apical aneurysm (LVAA). Methods: CMR confirmed 25 ApHCM patients complicating with LVAA from January 2010 to December 2017 in Fuwai hospital were included in this study, and the baseline clinical data and CMR characteristics were retrospectively analyzed. There were 14 pure ApHCM (hypertrophy limited at the apical segments) complicating with LVAA patients and 11 mixed ApHCM (predominantly apical hypertrophy along with thickening of contiguous non-apical left ventricular region) with LVAA patients. Results: In this patient cohort,age of 84% (21/25) patients ranged between 20-70 years old, and 68% (17/25) were male. There were 68% (17/25) patients with complaint of chest distress symptom, 56% (14/25) with complaint of chest pain, 32% (8/25) with complaint of palpitation,16% (4/25) with complaint of dyspnea, and 12% (3/25) presented as syncope. ST-T segment changes of electrocardiogram were observed in all patients, and giant negative T waves were detected in 80% patients (20/25). The rate of missed diagnosis by echocardiography for detecting ApHCM and LVAA was 16% (4/25) and 68% (17/25), respectively. CMR showed discrete thin-walled dyskinetic or akinetic segment of the most distal portion of the left ventricular chamber in ApHCM patients with LVAA. Transmural late gadolinium enhancement of the aneurysmal rim was detected in 76% (19/25) patients, and the maximum transverse dimension of aneurysm was bigger in patients with transmural late gadolinium enhancement than in patients without transmural late gadolinium enhancement ((22.0±10.8)mm vs. (11.7±4.0) mm, P=0.033). Conclusion: ApHCM with LVAA patients have distinct cardiac clinical features, and CMR is the most useful tool for the accurate and objective evaluation of this disease.

Moxifloxacin monotherapy for treatment of complicated intra-abdominal infections: a meta-analysis of randomised controlled trials.

To evaluate the efficacy and safety of moxifloxacin monotherapy for treatment of complicated intra-abdominal infections. PubMed, EMBASE, Science Direct, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials were searched to retrieve randomised controlled trials (RCTs) compared moxifloxacin monotherapy with other antibiotics in the treatment of complicated intra-abdominal infections from January 1999 to July 2011. A meta-analysis of all included randomised controlled trials was performed. Four randomised controlled trials including a total of 2444 patients with complicated intra-abdominal infections were included for meta-analysis. The results of the meta-analysis indicated that the moxifloxacin was associated with similar clinical cure rate (four RCTs, 1934 patients, OR = 0.80, 95% CI: 0.61, 1.04, p = 0.09), bacteriological success rates (four RCTs, 1484 patients, OR = 0.79, 95% CI: 0.59, 1.05, p = 0.11) and mortality (four RCTs, 2227 patients, OR = 0.91, 95% CI: 0.45, 1.83, p = 0.79) compared with the control group. The overall incidence of adverse events of moxifloxacin was significantly higher than that in the control group (three RCTs, 1367 patients, OR = 1.33, 95% CI: 1.07, 1.63, p = 0.008), although the incidence of drug-related adverse events (three RCTs, 1601 patients, OR = 1.13, 95% CI: 0.69, 1.85, p = 0.63) and serious adverse events (three RCTs, 1815 patients, OR = 1.23, 95% CI: 0.59, 2.60, p = 0.58) were similar between the compared treatment groups. Moxifloxacin is an effective and relatively safe option for the treatment of patients with intra-abdominal infections. Moxifloxacin monotherapy has similar efficacy to combination therapy.

High-resolution nonlinear optical imaging of live cells by second harmonic generation.

By adapting a laser scanning microscope with a titanium sapphire femtosecond pulsed laser and transmission optics, we are able to produce live cell images based on the nonlinear optical phenomenon of second harmonic generation (SHG). Second harmonic imaging (SHIM) is an ideal method for probing membranes of living cells because it offers the high resolution of nonlinear optical microscopy with the potential for near-total avoidance of photobleaching and phototoxicity. The technique has been implemented on three cell lines labeled with membrane-staining dyes that have large nonlinear optical coefficients. The images can be obtained within physiologically relevant time scales. Both achiral and chiral dyes were used to compare image formation for the case of single- and double-leaflet staining, and it was found that chirality plays a significant role in the mechanism of contrast generation. It is also shown that SHIM is highly sensitive to membrane potential, with a depolarization of 25 mV resulting in an approximately twofold loss of signal intensity.

Membrane electric properties by combined patch clamp and fluorescence ratio imaging in single neurons.

An experimental method has been established to measure the electric properties of a cell membrane by combination of patch clamp and dual-wavelength ratio imaging of a fluorescent potentiometric dye, 1-(3-sulfonatopropyl)-4-[beta[2-(di-n-octylamino)-6-naphthyl]vinyl ]pyridinium betaine (di-8-ANEPPS). Pairs of fluorescence images from the dye-stained membrane of neuroblastoma N1E-115 cells excited at two wavelengths were initially obtained to calculate ratio images corresponding to the resting transmembrane potential. Subsequently, a whole-cell patch was established and the membrane potential clamped to levels varying from -100 to +60 mV; at each voltage, a pair of dual-wavelength images were acquired to develop a calibration of the fluorescence ratio. Using this method, the resting potentials could accurately be measured showing that the differentiated cells were 17 mV more polarized than undifferentiated cells. The combination of electrical and optical methods can also follow changes in other membrane electric properties, such as dipole potential, and thus permit a detailed analysis of the membrane electrical properties underlying the voltage regulation of ion channels.

Distinct electric potentials in soma and neurite membranes.

Structurally similar voltage-dependent ion channels may behave differently in different locations along the surface of a neuron. A possible reason could be that channels experience nonuniform electrical potentials along the plasmalemma. Here, we map the electrical potentials along the membrane of differentiated N1E-115 neuroblastoma cells with a potential-sensitive dye. We find that the intramembrane potential gradient is indeed more positive in the membranes of neurites than in the membranes of somata. This is not attributable to differences in ion conductances or surface charge densities between the membranes of neurites and somata; instead, it can be explained by differences in lipid composition. The spatial variation in intramembrane electrical potential may help account for electrophysiological and functional differences between neurites and somata.

Simultaneous imaging of cell and mitochondrial membrane potentials.

The distribution of charged membrane-permeable molecular probes between intracellular organelles, the cytoplasm, and the outside medium is governed by the relative membrane electrical potentials of these regions through coupled equilibria described by the Nernst equation. A series of highly fluorescent cationic dyes of low membrane binding and toxicity (Ehrenberg, B., V. Montana, M.-D. Wei, J. P. Wuskell, and L. M. Loew, 1988. Biophys. J. 53:785-794) allows the monitoring of these equilibria through digital imaging video microscopy. We employ this combination of technologies to assess, simultaneously, the membrane potentials of cells and of their organelles in situ. We describe the methodology and optimal conditions for such measurements, and apply the technique to concomitantly follow, with good time resolution, the mitochondrial and plasma membrane potentials in several cultured cell lines. The time course of variations induced by chemical agents (ionophores, uncouplers, electron transport, and energy transfer inhibitors) in either or both these potentials is easily quantitated, and in accordance with mechanistic expectations. The methodology should therefore be applicable to the study of more subtle and specific, biologically induced potential changes in cells.

Membrane potential can be determined in individual cells from the nernstian distribution of cationic dyes.

The distribution of a selection of cationic fluorescent dyes can be used to measure the membrane potential of individual cells with a microfluorometer. The essential attributes of these dyes include membrane permeability, low membrane binding, spectral properties which are insensitive to environment, and, of course, strong fluorescence. A series of dyes were screened on HeLa cells for their ability to meet these criteria and several commercially available dyes were found to be satisfactory. In addition, two new dyes were synthesized for this work by esterification of tetramethyl rhodamine. The analysis of the measured fluorescent intensities requires correction for fluorescence collected from outside the plane of focus of the cell and for nonpotentiometric binding of the dye. The measurements and analysis were performed on three different cell types for which there exists a body of literature on membrane potential; the potentials determined in this work were always within the range of literature values. The rhodamine esters are nontoxic, highly fluorescent dyes which do not form aggregates or display binding-dependent changes in fluorescence efficiency. Thus, their reversible accumulation is quantitatively related to the contrast between intracellular and extracellular fluorescence and allows membrane potentials in individual cells to be continuously monitored.