Pulmonary artery stiffness in fetuses with tetralogy of Fallot.

PURPOSE: This study evaluated the elastic characteristics of the pulmonary trunk and distal branches in fetuses diagnosed with tetralogy of Fallot (TOF) using Doppler echocardiography. METHODS: Data on 42 fetuses diagnosed with TOF and 84 gestational age-matched normal fetuses were prospectively collected from the Second Xiangya Hospital of Central South University between August 2022 and January 2023. The severity of TOF was classified into three categories based on the z-score of the pulmonary annulus diameter: mild (z-score ≥-2), moderate (-40.05). CONCLUSION: Fetuses diagnosed with TOF exhibited increased vascular stiffness in the MPA and reduced stiffness in the distal pulmonary artery (PA). Larger-scale follow-up studies are required to elucidate the relationships between these changes in vascular stiffness and PA development in patients with TOF.

Assessment of Pulmonary Arterial Vascular Impedance in Fetuses With Tetralogy of Fallot.

OBJECTIVE: To evaluate the vascular impedance of the pulmonary arteries in fetuses with tetralogy of Fallot (TOF) by Doppler echocardiography. METHODS: A total of 42 fetuses with TOF (TOF group) and 84 gestational age-matched normal fetuses (control group) were prospectively collected from the Second Xiangya Hospital of Central South University from August 2022 to January 2023. The severity of TOF was classified into mild TOF (z score ≥-2), moderate TOF (-4 < z score < -2), or severe TOF (z score ≤-4) according to the z score value of the pulmonary annulus diameter. The pulsatility index (PI) of the main pulmonary artery (MPA), distal left pulmonary artery (DLPA), and distal right pulmonary artery (DRPA) were measured by pulsed-wave Doppler. The differences in clinical data and echocardiographic parameters between TOF group, control group, and TOF subgroups were compared. RESULTS: Compared with the control group, MPA-PI increased significantly, whereas DLPA-PI and DRPA-PI decreased in TOF group (all P < .001). There were no significant differences in MPA-PI and DRPA-PI among mild TOF, moderate TOF, and severe TOF (all P > .05). However, DLPA-PI decreased significantly in severe TOF compared with mild TOF (P < .05). CONCLUSION: Fetuses with TOF presented increased vascular impedance in the pulmonary trunk and decreased impedance in distal pulmonary artery branches. Further large and follow-up studies are needed to demonstrate the associations between those changed vascular impedances and the development of PA in patients with TOF.

Biomechanical properties of the ascending aorta in patients with arterial hypertension by velocity vector imaging.

Aortic stiffness is an important risk factor for cardiovascular events and morbidity. Increased aortic stiffness is associated with an increase in cardiac and vascular hypertension-related organ damage. To evaluate the biomechanical properties of the ascending aorta (AA) in patients with arterial hypertension (AH) by velocity vector imaging (VVI). Ninety-five patients with AH and 53 normal healthy control participants were prospectively enrolled. AA biomechanical properties, i.e., ascending aortic global longitudinal strain (ALS), ascending aortic global circumferential strain (ACS), and fractional area change (FAC), were evaluated by VVI. Relative wall thickness (RWT) and left ventricular mass (LVM) were calculated. Pulsed Doppler early transmitral peak flow velocity (E), early diastolic mitral annular velocity (e'), left ventricular global longitudinal strain (GLS), distensibility (D) and stiffness index (SI) of AA were also obtained. The ALS, ACS and FAC were significantly lower in the AH patients, especially in those with ascending aorta dilatation (AAD), than in the normal healthy control subjects. The patients with AAD had a higher E/e' ratio, RWT, LVM and SI and a lower GLS and D than patients without AAD and normal healthy volunteers (p < 0.05). There were significant associations between biomechanical properties and D, SI, E/e' and GLS (ALS and D: r = 0.606, ALS and SI: r = - 0.645, ALS and E/e': r = - 0.489, ALS and GLS: r = 0.466, ACS and D: r = 0.564, ACS and SI: r = - 0.567, ACS and E/e': r = - 0.313, ACS and GLS: r = 0.320, FAC and D: r = 0.649, FAC and SI: r = - 0.601, FAC and E/e': r = - 0.504, FAC and GLS: r = 0.524, respectively, p < 0.05). The biomechanical properties of AA were impaired in patients with AH, especially patients with ascending aorta dilatation. Hypertension is associated with a high prevalence of diastolic and systolic dysfunction and increased arterial stiffness. Further study is needed to evaluate the clinical application of AA biomechanical properties by VVI.

Impaired Distensibility of the Proximal Aorta in Fetuses With Tetralogy of Fallot.

Background Increased aortic wall stiffness, which even persists after repair, has been reported in patients with tetralogy of Fallot (TOF). We aimed to observe the distensibility of the ascending aorta and descending aorta in fetuses with TOF and explore its relation with aortic blood flow volume and aortic and pulmonary annular size. Methods and Results Twenty-three fetuses with TOF and 23 gestational age-matched normal fetuses were included in this prospective cross-sectional study. The distensibilities of the ascending aorta and descending aorta were assessed by aortic strain (AS), which was defined as follows: 100×(maximum internal diameter in the systolic phase-minimum internal diameter in the diastolic phase)/minimum internal diameter in the diastolic phase. The maximum internal diameter in the systolic phase and minimum internal diameter in the diastolic phase of the ascending aorta and descending aorta were measured by M-mode echocardiography. Associations between AS and aortic blood flow volume and aortic and pulmonary valve diameters were assessed in both groups. AS of the ascending aorta in TOF group was lower than that in controls (20.48%±4.19% versus 28.17%±4.54%; P<0.001), whereas there was no significant difference in the descending aorta. The multivariate regression model demonstrated that AS was significantly related to aortic valve size (P=0.014) and aortic blood flow volume (P=0.022) in fetuses with TOF, whereas only aortic blood flow volume was significantly correlated with AS in the control group (P=0.01). No significant association was found between AS and pulmonary valve size. Conclusions Impaired distensibility of proximal aorta was observed in fetuses with TOF. Both intrinsic abnormalities of the aortic wall and aortic volume overload probably play roles in the altered aortic distensibility.

Unusual presentation of a case of fetal hepatic mass: a case report.

BACKGROUND: Giant hepatic hemangiomas are rare and can cause serious complications that contribute to a high risk of perinatal mortality. The purpose of this article is to review the prenatal imaging features, treatment, pathology, and prognosis of an atypical fetal giant hepatic hemangioma and to discuss the differential diagnosis of fetal hepatic masses. CASE PRESENTATION: A gravida 9, para 0 woman at 32 gestational weeks came to our institution for prenatal ultrasound diagnosis. A complex, heterogeneous hepatic mass measuring 5.2 × 4.1 × 3.7 cm was discovered in the fetus using conventional two-dimensional ultrasound. The mass was solid and had both a high peak systolic velocity (PSV) of the feeding artery and intratumoral venous flow. Fetal magnetic resonance imaging (MRI) revealed a clear, hypointense T1-W and hyperintense T2-W solid hepatic mass. Prenatal diagnosis was very difficult due to the overlap of benign and malignant imaging features on prenatal ultrasound and MRI. Even postnatally, neither contrast-enhanced MRI nor contrast-enhanced computed tomography (CT) was useful in accurately diagnosing this hepatic mass. Due to persistently elevated Alpha-fetoprotein (AFP), a laparotomy was performed. Histopathological examination of the mass showed atypical features such as hepatic sinus dilation, hyperemia, and hepatic chordal hyperplasia. The patient was ultimately diagnosed with a giant hemangioma, and the prognosis was satisfactory. CONCLUSIONS: When a hepatic vascular mass is found in a third trimester fetus a hemangioma should be considered as a possible diagnosis. However, prenatal diagnosis of fetal hepatic hemangiomas can be challenging due to atypical histopathological findings. Imaging and histopathological assays can provide useful information for the diagnosis and treatment of fetal hepatic masses.

Case Report: Prenatal Diagnosis of Nemaline Myopathy.

Nemaline myopathy (NM) is a rare, hereditary heterogeneous myopathy. Fetal NM has a more severe disease course and a poorer prognosis and is usually lethal during the first few months of life. Hence, early prenatal diagnosis is especially important for clinical interventions and patient counseling. We report the case of a fetus with NM due to KLHL40 gene variation leading to arthrogryposis multiplex congenita (AMC). The ultrasonography and histopathology results revealed an enhanced echo intensity and decreased muscle thickness, which may be novel features providing early clues for the prenatal diagnosis of NM. Moreover, to our knowledge, this article is the first report to describe a case of NM associated with complex congenital heart disease (CHD).

Aortic Elasticity and Cardiac Function in Fetuses With Aortic Coarctation.

Objective: The purpose of the study was to observe the elasticity of the ascending aorta (AAo) in normal fetuses and fetuses with coarctation of the aorta (CoA) by M-mode echocardiography. Methods: This was a prospective clinical study performed on 16 fetuses with CoA and 48 gestational-age matched normal fetuses. The minimum internal diameter in the diastolic phase (Dmin) and the maximum internal diameter in the systolic phase (Dmax) of the AAo were measured by M-mode echocardiography. The aortic strain was calculated using the formula 100 × (Dmax-Dmin)/Dmin). Doppler echocardiography was performed to measure the cardiac function parameters. Correlations between aortic strain and cardiac function were assessed in fetuses with CoA. Results: The aortic strain of the ascending aorta in the fetuses with CoA was significantly lower than that in normal fetuses (18.12 ± 4.88% vs. 25.22 ± 4.92%, p < 0.01). The fetuses with CoA showed significantly higher combined cardiac output than the controls (471.89 ± 93.98 vs. 411.57 ± 46.35 ml/min/kg, p < 0.05). Compared with the normal group, the early diastolic velocities (E') and peak systolic velocities (S') of the left side were obviously decreased in the CoA group (p < 0.05), while the left early diastolic velocity ratio (E/E') was significantly increased in the fetuses with CoA (p < 0.01). For the fetuses with CoA, the aortic strain of the AAo was correlated with the left E/E' and S' (r = -0.522 and 0.504, respectively, P < 0.05). Conclusions: The aortic strain of the ascending aorta was significantly decreased in fetuses with CoA in middle-late gestation. The impaired strain of the ascending aorta was correlated with the left ventricle function in the fetuses with CoA. These findings imply that the abnormalities of the intrinsic aortic wall of CoA might develop early in utero.

Heart-targeted amelioration of sepsis-induced myocardial dysfunction by microenvironment responsive nitric oxide nanogenerators in situ.

BACKGROUND: A balanced endogenous level of bioavailable nitric oxide (NO) plays a key role in maintaining cardiovascular homeostasis. The bioactive NO level in the cardiomyocytes was much reduced during sepsis. However, it is clinically challenging for the NO gas therapy due to the lack of spatial and temporal release system with precise control. The purpose of this study is to design a NO-releasing biomaterial with heart-targeted capability responsive to the infectious microenvironment, thus ameliorating lipopolysaccharide (LPS)-induced cardiac dysfunction. RESULTS: The heart-targeted NO delivery and in situ releasing system, PCM-MSN@LA, was synthesized using hollow mesoporous silica nanoparticles (MSN) as the carrier, and L-arginine (LA) as the NO donor. The myocardial delivery was successfully directed to heart by specific peptide (PCM) combined with low-intensity focused ultrasound (LIFU) guidance. The myocardial system synthesized NO from the LA released from PCM-MSN@LA in the presence of increased endogenous nitric oxide synthase (NOS) activity induced by LPS. This targeted NO release in situ achieved extraordinary protective effects against LPS-challenged myocardial injury by reducing the recruitment of inflammatory cells, inhibiting oxidative stress and maintaining the mitochondria integrity. In particular, this protection was not compromised by simultaneous circulation collapse as an adverse event in the context. CONCLUSIONS: PCM-MSN@LA + LIFU exhibited extraordinary cardioprotective effects against severe sepsis in the hearts of LPS-treated animals without the side effect of NO diffusion. This technology has great potential to be served as a novel therapeutic strategy for sepsis-induced myocardial injury.

Z-Score Reference Ranges for Umbilical Vein Diameter and Blood Flow Volume in Normal Fetuses.

OBJECTIVES: To establish Z-scores for the diameter and blood flow volume of the umbilical vein (UV) in normal fetuses. METHODS: This was a prospective study involving 907 normal fetuses. We measured the diameter (Duv) of two different segments of the UV (FUV: the free loop of the UV; FIUV: the fetal intra-abdominal UV). Next, we calculated the blood flow volume (Quv). Z-scores were created for both Duv and Quv using gestational age, femur length, and biparietal diameter as independent variables. RESULTS: We successfully acquired 858 (94.6%) normal fetal measurements. Between 20 and 39 weeks, the Duv of the FUV and FIUV increased from 0.38 to 0.80 cm and from 0.33 to 0.70 cm, respectively. The Quv of the FUV and FIUV increased from 32.66 to 381.88 ml/min and from 31.50 to 360.15 ml/min, respectively. Linear or quadratic regression models were best fitted between the parameters of UV and the independent variables. Z-scores were successfully determined for both the Duv and Quv. CONCLUSIONS: The calculation of Z-scores for the Duv and Quv is simple by applying standard statistical methods. These Z-scores may be useful to evaluate placental circulation and provide a rationale for monitoring and evaluating the prognosis of fetuses.

Evaluation of fetal foramen ovale blood flow by pulsed Doppler ultrasonography combined with spatiotemporal image correlation : To define the normal reference range of fetal foramen ovale blood volume for each gestational age: a cross-sectional study.

OBJECTIVE: The objective of this study was to determine fetal foramen ovale blood flow utilizing pulsed Doppler combined with spatiotemporal image correlation. METHODS: A cross-sectional study was performed in 440 normal fetuses between 20 and 40 weeks of gestation. In order to calculate foramen ovale blood flow, the foramen ovale flow velocity-time integral was obtained by pulsed Doppler ultrasonography, and the foramen ovale area was measured by using spatiotemporal image correlation rendering mode. Foramen ovale blood flow was calculated as the product of the foramen ovale area and the velocity-time integral. RESULTS: Gestational age-specific reference ranges are given for the absolute blood flow (ml/min) of foramen ovale, showing an exponential increase from 20 to 30 weeks of gestation, and a flat growth trend during the last trimester, while the weight-indexed flow (ml/min/kg) of foramen ovale decreased significantly. The median weight-indexed foramen ovale blood flow was 320.82 ml/min/kg (mean 319.1 ml/min/kg; SD 106.33 ml/min/kg). CONCLUSIONS: The reference range for fetal foramen ovale blood flow was determined from 20 to 40 weeks of gestation. The present data show that the volume of foramen ovale blood flow might have a limited capacity to increase during the last trimester.

Chinese Expert Consensus on Protection for Ultrasound Healthcare Workers against COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a worldwide pandemic and poses a serious public health risk. It has been proven that lung ultrasound can be extremely valuable in the diagnosis and treatment of the disease, which could also minimize the number of exposed healthcare workers and equipment. Because healthcare workers in ultrasound departments are in close contact with patients who might be infected or virus carriers, it is extremely important that they be provided sufficient protection. Extremely aggressive protection should be avoided because it might lead to a lack of protection equipment for the hospital. Guidance on proper protection management should be provided in detail, for example, how to choose personal protective equipment, how to disinfect the environment. To address these problems, on behalf of the Chinese Ultrasound Doctors Association, Chinese PLA Professional Committee of Ultrasound in Medicine, Beijing Institute of Ultrasound in Medicine and Chinese Research Hospital Association Ultrasound Professional Committee, the authors have summarized the recommendations for effective protection according to existing hygienic standards, their experience and available literature. After the recommendations were completed, two online conferences were held on January 31, 2020 and February 7, 2020, at which the recommendations were discussed in detail. A modified version of the work was circulated and finally approved by all authors, and is the present Chinese Expert Consensus on Protection for Ultrasound Healthcare Workers against COVID-19.

[Protective effects of myocardium-targeted nanoparticles loaded L-arginineon on sepsis-induced myocardial injury].

OBJECTIVE: To prepare primary cardiomyocyte (PCM) specific peptide-conjugated mesoporous silicon nanoparticles (MSN) with L-arginine (LA) as a core (PCM-MSN@LA), and evaluate its specific protective effect on septic myocardium. METHODS: PCM-MSN@LA was prepared by condensation reaction, the characterization of PCM-MSN@LA, the amount of LA modification and release was detected, and the phagocytosis of PCM-MSN@LA and its affinity to myocardial tissue was observed. (1) Experiment one: SD neonatal rat cardiomyocytes were divided into control group (Con group), lipopolysaccharide (LPS) group, MSN@LA/LPS group and PCM-MSN@LA/LPS group. The LPS group was stimulated with 5 mg/L LPS for 16 hours, while the MSN@LA/LPS group and PCM-MSN@LA/LPS group were treated with 5 mg/L LPS and 25 mg/L LA-containing nanoparticles (MSN@LA and PCM-MSN@LA) for 16 hours. Cell viability and reactive oxygen species (ROS) production levels were detected. Apoptosis was observed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL). Western Blot was used to detect the changes in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) proteins. (2) Experiment two: 64 healthy male C57BL/6 mice were divided into Sham group, LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group by random number table method, 16 mice in each group. LPS group were injected 50 mg/kg LPS intraperitoneally. MSN@LA/LPS group and PCM-MSN@LA/LPS group were injected with 0.5 mg/kg MSN@LA and PCM-MSN@LA via tail vein immediately after intraperitoneal injection of LPS. Eight animals in each group were used to observe the 24-hour survival rate, and the other 8 mice were used to detect cardiac function by echocardiography at 12 hours after operation; mRNA expressions of interleukin (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) were measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). RESULTS: PCM-MSN@LA was spherical, with particle size of about 180 nm, Zeta potential of about -21 mV, with LA loaded. The amount of LA modification and release rate were 12.3% and 24.3%, respectively. Cell phagocytosis experiments showed that PCM-MSN@LA had the targeting ability of cardiomyocytes and myocardial tissue. Experiment one: after LPS stimulation of myocardial cells, cell viability decreased, while ROS generation, apoptosis, eNOS and iNOS protein expressions increased. Compared with LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group had higher cell viability, reduced ROS levels and apoptosis, increased expressions of eNOS and iNOS. PCM-MSN@LA/LPS group changed the above effect further than MSN@LA/LPS group [cell viability (A value): 0.51±0.08 vs. 0.41±0.03, ROS (relative fluorescence intensity): 28 450±1 941 vs. 35 628±2 551, TUNEL positive cells/total cells: 0.27±0.03 vs. 0.35±0.04, eNOS/ß-Tubulin: 1.467±0.046 vs. 1.201±0.131, iNOS/ß-Tubulin: 1.700±0.033 vs. 1.577±0.068, all P < 0.05]. Experiment two: the number of 24-hour survive in MSN@LA/LPS group and PCM-MSN@LA/LPS group were higher than LPS group (number: 2, 4 vs. 1, P values were 0.36 and 0.03 respectively). Compared with Sham group, the cardiac function of LPS group was significantly inhibited and the mRNA expression of inflammatory factors increased. The PCM-MSN@LA/LPS group had higher left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (LVFS) than LPS group, and lower mRNA expressions of IL-1, IL-6, and TNF-α mRNA [LVEF: 0.456±0.019 vs. 0.337±0.017, LVFS: (21.97±1.78)% vs. (15.53±1.67)%, IL-1 mRNA (2-ΔΔCT): 169.22±8.95 vs. 189.79±6.79, IL-6 mRNA (2-ΔΔCT): 19.90±1.60 vs. 23.74±1.45, TNF-α mRNA (2-ΔΔCT): 8.21±0.81 vs. 11.00±1.48, all P < 0.05]. There was no significant difference in each index between the MSN@LA/LPS group and LPS group. CONCLUSIONS: PCM-MSN@LA with myocardial targeting characteristic significantly increased the activity of myocardial cells, down-regulated the expression of inflammatory factors and the production of ROS, alleviated cardiac insufficiency in sepsis, and achieved the targeted treatment of myocardial injury in sepsis.

Antitumor effects of Sweroside in human glioblastoma: its effects on mitochondrial mediated apoptosis, activation of different caspases, G0/G1 cell cycle arrest and targeting JNK/p38 MAPK signal pathways.

PURPOSE: Glioblastoma is one of the prevalent types of brain tumors and is responsible for significant number of deaths world over. Glioblastoma is often diagnosed at advanced stages and there are frequent relapses following chemotherapy. Herein, we examined the anticancer effects of a secoiridoid glycoside Sweroside, against a panel of glioblastoma cells. METHODS: CCK8 assay was used to examine the anti-proliferative effects of this molecule. Αcridine orange (AO)/ethidium bromide (EB) and annexin V/propidium iodide (PI) staining assays were used to examine apoptotic cell death. Cell cycle analysis was performed by flow cytometry. The protein expression was examined by western blotting. RESULTS: Sweroside inhibited the growth of the glioblastoma U251 cell with IC50 of 10 µM. However, Sweroside had low cytotoxic effects on the normal astrocytes cells with an IC50 of 100 µM. Sweroside exerted antiproliferative effects on the U251 glioblastoma cells by apoptotic cell death. This was concomitant with upregulation of apoptotic proteins such as caspase 3 and 9, and Bax expressions. Sweroside also induced arrest of the U251 cells at the G0/G1 phase of the cell cycle. Finally, Sweroside also blocked the JNK/p38 MAPK signal pathway concentration-dependently in U251 glioblastoma cells. CONCLUSIONS: Taken together, these results suggest that Sweroside exerts potent anticancer effects on glioblastoma cells and may prove essential in the management of glioblastoma.

l-Cysteine augments microtubule-associated protein 2 levels and enhances antioxidant activity in rats following traumatic brain injury.

l-Cysteine is a well-known sulfur-containing non-essential amino acid that can be oxidized to cysteine, which possesses a variety of pharmacological actions, including antioxidant and anti-inflammatory activities. Traumatic brain injury (TBI) is defined as a closed head injury that leads to temporary alterations in neural function and further leads to pathophysiological processes. In the present study, rats were categorized into sham, control, 100 mg/kg l-cysteine, and 200 mg/kg l-cysteine groups and then the levels of lipid peroxidation, reduced glutathione (GSH), catalase, superoxide dismutase (SOD), reactive oxygen species (ROS), and mRNA and protein expression of microtubule-associated protein 2 (MAP2) were determined. Following supplementation with l-cysteine, there were reductions in lipid peroxidation and ROS levels, whereas catalase, SOD, and GSH levels increased. Additionally, the mRNA expression of MAP2 in the control rats was drastically reduced by 67% compared to the sham rats. However, supplementation with 100 mg/kg of l-cysteine and 200 mg/kg of l-cysteine significantly increased MAP2 mRNA expression by 84.8% and 169.7%, respectively. Similarly, MAP2 protein expression was drastically reduced by 61% in control rats compared to sham rats, but supplementation with 100 mg/kg of l-cysteine and 200 mg/kg of l-cysteine significantly increased MAP2 protein expression by 41% and 94.9%, respectively. Taken together, these data suggest that supplementation with l-cysteine significantly reduced lipid peroxidation and ROS levels, but increased antioxidant levels and the mRNA and protein expression of MAP2 in rats following TBI.

MicroRNA-362-3p Targets PAX3 to Inhibit the Development of Glioma through Mediating Wnt/ß-Catenin Pathway.

BACKGROUND: Glioma is identified as a broad category of brain and spinal cord tumors. MiR-362-3p is important in regulating the genesis of different cancers; however, the mechanism of miR-362-3p in the progression of glioma remains largely unknown. OBJECTIVES: This study aimed to elucidate pathobiological functions of miR-362-3p by targeting PAX3 in glioma. METHOD: qRT-PCR and western blotting were used to examine miR-362-3p and PAX3 expression in glioma tissues and cells. CCK-8 assay and transwell assays were used to examine the functions of miR-362-3p on human glioma. Two bioinformatics analysis software and luciferase reporter assay were performed to analyze the relationship between miR-362-3p and PAX3. RESULTS: MiR-362-3p was downregulated, and PAX3 was upregulated in glioma tissues and cells. Functional assays revealed that ectopic expression of miR-362-3p inhibited glioma cell proliferation and migration. Further, PAX3 was confirmed as direct target gene of miR-362-3p, and downregulation of PAX3 reversed the suppressive effects of miR-362-3p in glioma. In addition, miR-362-3p also exhibited suppressive effect on epithelial-mesenchymal transition and Wnt/ß-catenin pathway. CONCLUSIONS: MiR-362-3p downregulation or PAX3 overexpression predicted poor prognosis in glioma. MiR-362-3p played a role in the suppressive effect on glioma by targeting PAX3 through suppressing Wnt/ß-catenin pathway.

Prenatal diagnosis of fetal intraabdominal extralobar pulmonary sequestration: a 12-year 3-center experience in China.

To provide useful information for diagnosing and predicting fetal intraabdominal extralobar pulmonary sequestration (IEPS), a retrospective review of diagnostic approaches was conducted. Ultrasonography was performed serially in 21 fetuses with IEPS from 2005 to 2017. Prenatal sonographic features, treatment, and outcomes of each case were evaluated and collected. These cases of IEPS were also compared to 43 cases previously reported by other researchers from 1986 to 2017. Of the 21 sonographic features, 14 (67%) were hyperechoic, 21 (100%) were well circumscribed, and 17 (81%) depicted a mass that shifted with fetal breaths/hiccups non-synchronized with adjacent organs (sliding sign). Feeding arteries were detected prenatally in 18 patients (86%). The lesion volume was 10.17 ± 4.66 cm3, the congenital cystic adenomatoid malformation volume ratio and cardiothoracic ratio were in normal range. The gestational age at diagnosis, location and echotexture of the lesion, and rate of surgical treatment were similar to previous studies, but with a significantly higher rate of detected feeding arteries (P < 0.01), and associated anomalies (P < 0.01). All infants who underwent surgery after birth had satisfactory outcomes. The sliding sign and feeding artery are essential features of IEPS in prenatal diagnosis.

[Blood flow parameters in fetal anterior cerebral artery during the second and third trimester of gestation].

OBJECTIVE: To investigate hemodynamic parameters in 2 anatomical segments (S1 and S2) of anterior cerebral artery (ACA) in normal pregnancy during the second and third trimester of gestation.
 Methods: The peak systolic velocity (PSV), end diastolic velocity (EDV), time-average maximum velocity (TAMAXV), peak systolic velocity/end diastolic velocity (S/D), resistance index (RI), and pulsation index (PI) in S1 and S2 of fetal anterior cerebral artery (ACA) in 288 normal pregnant women were detected by power Doppler and pulsed Doppler. Multiple regression models were fitted to estimate the relation between Doppler variables and gestational age. The differences of hemodynamic parameters between ACAS1 and ACAS2 were compared.
 Results: The PSV, EDV, and TAMAXV of ACAS1 and ACAS2 were positively correlated with the weeks of pregnancy (P<0.001), all fitted with the cubic curve. The S/D, PI, and RI values of ACAS1 and ACAS2 were not correlated with gestational ages (P>0.05). The PSV, TAMAXV, S/D, PI, and RI of ACAS1 were significantly higher than those of ACAS2, while EDV in ACAS1 was lower than that in ACAS2 (P<0.05).
 Conclusion: The velocity parameters (PSV, EDV, TAMAXV) of the 2 anatomical segments (ACAS1 and ACAS2) are increased with the increase of gestational age in normal pregnant fetus during the second and third trimester of gestation, and the resistance parameters (S/D, PI, RI) are not significantly correlated with gestational age. Distribution of blood flow is different in the blood supply territory between ACAS1 and ACAS2.

Importance of the Complement Alternative Pathway in Serum Chemotactic Activity During Sepsis.

Serum chemotactic activity is important in regulating neutrophil migration. The ability of neutrophils to migrate to infectious site is crucial for host effective pathogen control, but unregulated neutrophil activation can also cause tissue damage. During bacterial sepsis, the complement alternative pathway (AP) is massively activated in blood and tissues and reportedly contributes to sepsis pathogenesis. Complement factor B (FB) is an essential component of the AP activation. However, the impact of FB/AP activation on blood chemotactic activity during bacterial infection is unclear. In this study, we found that sera of septic mice following cecal ligation and puncture (CLP) had much higher chemotactic activities on neutrophils than those of sham animals. Compared with wild-type (WT) mice, FB mice had significantly attenuated serum chemotactic activity, under both nonseptic and septic conditions. Moreover, sera with the activated AP by zymosan and cobra venom factor (CVF) in vitro induced a significant increase in neutrophil migration compared with sera without the AP activation. Complement activation generates complement cleavage fragment such as Ba, C3a, and C5a. To delineate the contribution of these downstream effectors, we incubated AP-active sera (AP activated by zymosan/CVF) or sera from sham and septic mice with anti-C5a or mAb1379 (anti-Ba) neutralizing antibody. We found that anti-C5a, but not mAb1379, markedly attenuated the neutrophil chemotactic effect of the AP-activated sera and that of septic sera. Taking together, these data suggest that the complement AP activation during bacterial sepsis plays a pivotal role in promoting blood chemotactic activity through a C5a-dependent mechanism.

Lipopeptide PAM3CYS4 Synergizes N-Formyl-Met-Leu-Phe (fMLP)-Induced Calcium Transients in Mouse Neutrophils.

N-Formyl-Met-Leu-Phe (fMLP), a mimic of N-formyl oligopeptides that are released from bacteria, is a potent leukocyte chemotactic factor. It induces intracellular calcium ([Ca]i) transient that is important for various neutrophil biological functions, e.g., adhesion, ROS, and cytokine productions. Toll-like receptors (TLRs), an essential part of host innate immunity, regulate neutrophil activities, but their role in [Ca]i signaling is less clear. In the present study, we examined the effect of several TLR ligands, including Pam3Cys4 (TLR1/2), lipopolysaccharide (LPS, TLR4), and lipoteichoic acid (LTA, TLR2/6), on calcium signaling and on the fMLP-induced [Ca]i transients in mouse neutrophils loaded with Fura-2/AM. We found that unlike fMLP, the three TLR ligands tested did not elicit any detectable Ca flux. However, Pam3Cys4, but not LPS or LTA, markedly synergized the fMLP-induced [Ca]i transients, and had no effect on the host component keratinocyte-derived cytokine (KC)- or C5a-induced calcium flux. The effect of Pam3Cys4 on the fMLP-induced [Ca]i transients is by enhancing extracellular Ca influx, not intracellular Ca release. Surprisingly, deletion of TLR2 or MyD88 in neutrophils had no impact on the Pam3Cys4's effect, suggesting a TLR2-MyD88-independent mechanism. Finally, using the pan PKC activator and inhibitor, we demonstrated that PKC negatively regulated fMLP-induced [Ca]i transients and that inhibition of PKC did not prohibit Pam3Cys4's synergistic effect on the fMLP-induced calcium influx. In conclusion, the present study identified a novel synergistic effect of Pam3Cys4 on fMLP-induced [Ca]i transients, a process important for many neutrophil biological functions.