Acceleration index predicts efficacy of orthostatic training on postural orthostatic tachycardia syndrome in children.

The objective of this study was to examine the utility of the acceleration index observed in an electrocardiogram (ECG) for the prediction of the effectiveness of orthostatic training in pediatric patients diagnosed with postural orthostatic tachycardia syndrome (POTS). This investigation focused on children diagnosed with POTS and undergoing orthostatic training at the Department of Pediatrics of Peking University First Hospital from January 2012 to October 2022. Specifically, patients hospitalized from January 2012 to December 2019 were included in the training set (54 cases), while those hospitalized from January 2020 to October 2022 were included in the external validation set (37 cases). All children received a 3-month orthostatic training, and the baseline symptom score (SS) was calculated in agreement with the pretreatment orthostatic intolerance symptom frequency. Additionally, we determined post-treatment SS during follow-up via telephone after the 3-month treatment. Children with a decrease in post-treatment SS by ≥ 50% of the baseline were considered as responders; otherwise, they were considered as non-responders. Demographic data (age, sex, and body mass index), hemodynamic parameters (supine blood pressure, time to achieve a positive standing test, maximum increase in heart rate during the standing test, maximal heart rate reached during the standing test, and blood pressure at the point of maximal heart rate during the standing test), and electrocardiographic parameters (RR interval in the supine position, shortest RR interval in the upright position, and acceleration index) were collected from all the children prior to treatment. Univariate and multivariate regression analysis were conducted to investigate factors associated with the efficacy of orthostatic training. The predictive value of these indicators for the therapeutic effectiveness of orthostatic training in children with POTS was evaluated using receiver operating characteristic (ROC) analysis, and the indicators were validated using the validation set. Among the 54 children in the training set, 28 responded to orthostatic training, and 26 were nonresponsive. Compared with the non-responders, the responders demonstrated a significant reduction in acceleration index (P < 0.01). The ROC curve for the predictive value of the acceleration index exhibited an area under the curve = 0.81 (95% confidence interval: 0.685-0.926). With the acceleration index threshold < 27.93%, the sensitivity and specificity in the prediction of orthostatic training efficacy among children with POTS were 85.7% and 69.2%, respectively. The external validation results demonstrated that using acceleration index < 27.93% as the threshold, the sensitivity, specificity, and accuracy of predicting orthostatic training efficacy among children with POTS were 89.5%, 77.8%, and 83.8%, respectively. CONCLUSIONS: Electrocardiographic acceleration index can be used to predict the effectiveness of orthostatic training in treating children with POTS. WHAT IS KNOWN: • Postural orthostatic tachycardia syndrome (POTS) is a chronic orthostatic intolerance involving multiple mechanisms. Autonomic dysfunction is one of the main mechanisms of POTS in children and could be treated with orthostatic training. • In order to improve the efficacy of orthostatic training in children with POTS, it is particularly important to identify the patients with autonomic dysfunction as the main mechanism before the treatment. WHAT IS NEW: • We found acceleration index of the electrocardiogram (ECG) can be used as a satisfactory index to predict the efficacy of orthostatic training in the treatment of POTS in children. • Using the acceleration index to predict the efficacy of orthostatic training on POTS in children is easy to be popularized in hospitals at all levels because it is non-invasive, convenient, and not expensive.

Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study.

Serum uric acid (UA) level has been proven to be related to several cardiovascular and metabolic diseases. In the present study, we examined if baseline serum UA level could predict the therapeutic efficacy of midodrine hydrochloride on vasovagal syncope (VVS) in children. The pediatric VVS patients who received midodrine hydrochloride from November 2008 to October 2022 were enrolled. After a median treatment duration of 3 months, the therapeutic effect was evaluated. According to the patients' responses to midodrine hydrochloride, which was determined by the recurrence of syncope, they were divided into effective and ineffective groups. The baseline variables were explored using univariable and multivariate logistic analysis. The predictive efficacy was assessed by receiver operating characteristic curve (ROC), precision-recall curve (PR), Hosmer-Lemeshow test, calibration curve, and decision curve analysis (DCA). Totally, 53 participants were included in the study. Among the 51 patients who were successfully followed up, 29 (56.9%) responded to midodrine hydrochloride (effective group), and the other 22 (43.1%) failed to respond to midodrine hydrochloride (ineffective group). The participants in effective group had lower baseline serum UA level than those in ineffective group (276.5 ± 73 µmol/L vs. 332.7 ± 56 µmol/L, p = 0.004). Multivariable logistic analysis showed that serum UA was associated with the therapeutic response (odds ratio (OR): 0.985, 95% confidence interval (CI): 0.974-0.997, p = 0.01). ROC analysis indicated that using baseline serum UA < 299 µmol/L as a threshold value yielded a sensitivity of 77.3% and a specificity of 79.3% in predicting the treatment response to midodrine hydrochloride. The area under the PR curve was 0.833. Hosmer-Lemeshow test yielded a p value of 0.58, and calibration plot indicated that the model was well-fitted. DCA demonstrated that treatment decision depending on the baseline serum UA level resulted in a favorable net benefit.   Conclusion: This pilot study suggested that the baseline serum UA level could be taken as a predictor of therapeutic effect of midodrine hydrochloride on VVS in children. What is Known: • Empirical and unselected use of midodrine hydrochloride has an unfavorable therapeutic effect on VVS in children. Serum uric acid (UA) is closely linked to cardiovascular events. What is New: • A low baseline serum UA level successfully predicts the therapeutic effectiveness of midodrine hydrochloride on VVS in children.

The diagnosis and treatment of pediatric clinical myocarditis in China: a multicenter retrospective study.

This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. CONCLUSION: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. WHAT IS KNOWN: • Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. WHAT IS NEW: • To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis.

Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

Interaction among Hydrogen Sulfide and Other Gasotransmitters in Mammalian Physiology and Pathophysiology.

Hydrogen sulfide (H2S), nitric oxide (NO), carbon monoxide (CO), and sulfur dioxide (SO2) were previously considered as toxic gases, but now they are found to be members of mammalian gasotransmitters family. Both H2S and SO2 are endogenously produced in sulfur-containing amino acid metabolic pathway in vivo. The enzymes catalyzing the formation of H2S are mainly CBS, CSE, and 3-MST, and the key enzymes for SO2 production are AAT1 and AAT2. Endogenous NO is produced from L-arginine under catalysis of three isoforms of NOS (eNOS, iNOS, and nNOS). HO-mediated heme catabolism is the main source of endogenous CO. These four gasotransmitters play important physiological and pathophysiological roles in mammalian cardiovascular, nervous, gastrointestinal, respiratory, and immune systems. The similarity among these four gasotransmitters can be seen from the same and/or shared signals. With many studies on the biological effects of gasotransmitters on multiple systems, the interaction among H2S and other gasotransmitters has been gradually explored. H2S not only interacts with NO to form nitroxyl (HNO), but also regulates the HO/CO and AAT/SO2 pathways. Here, we review the biosynthesis and metabolism of the gasotransmitters in mammals, as well as the known complicated interactions among H2S and other gasotransmitters (NO, CO, and SO2) and their effects on various aspects of cardiovascular physiology and pathophysiology, such as vascular tension, angiogenesis, heart contractility, and cardiac protection.

Macrophage-derived sulfur dioxide is a novel inflammation regulator.

Macrophage-mediated inflammation is a key pathophysiological component of cardiovascular diseases, but the underlying mechanisms by which the macrophage regulates inflammation have been unclear. In our study, we, for the first time, showed an endogenous sulfur dioxide (SO2) production in RAW267.4 macrophages by using HPLC and SO2-specific fluorescent probe assays. Moreover, the endogenous SO2 generating enzyme aspartate aminotransferase (AAT) was found to be expressed by the macrophages. Furthermore, we showed that AAT2 knockdown triggered spontaneous macrophage-mediated inflammation, as represented by the increased TNF-α and IL-6 levels and the enhanced macrophage chemotaxis; these effects could be reversed by the treatment with a SO2 donor. Mechanistically, AAT2 knockdown activated the NF-κB signaling pathway in macrophages, while SO2 successfully rescued NF-κB activation. In contrast, forced AAT2 expression reversed AngII-induced NF-κB activation and subsequent macrophage inflammation. Moreover, treatment with a SO2 donor also alleviated macrophage infiltration in AngII-treated mouse hearts. Collectively, our data suggest that macrophage-derived SO2 is an important regulator of macrophage activation and it acts as an endogenous "on-off switch" in the control of macrophage activation. This knowledge might enable a new therapeutic strategy for cardiovascular diseases.

Negative auto-regulation of sulfur dioxide generation in vascular endothelial cells: AAT1 S-sulfenylation.

Recently, endogenous sulfur dioxide (SO2) has been found to exert an important function in the cardiovascular system. However, the regulatory mechanism for SO2 generation has not been entirely clarified. Hence, we aimed to explore the possible auto-regulation of endogenous SO2 generation and its mechanisms in vascular endothelial cells. We showed that SO2 did not affect the protein expression of aspartate aminotransferase 1 (AAT1), a major SO2 synthesis enzyme, but significantly inhibited AAT activity in primary human umbilical vein endothelial cells (HUVECs) and porcine purified AAT1 protein. An AAT1 enzymatic kinetic study showed that SO2 reduced the Vmax (1.89 ± 0.10 vs 2.55 ± 0.12, µmol/mg/min, P < 0.05) and increased the Km (35.97 ± 9.54 vs 19.33 ± 1.76 µmol/L, P < 0.05) values. Furthermore, SO2 induced S-sulfenylation of AAT1 in primary HUVECs and purified AAT1 protein. LC-MS/MS analysis indicated that SO2 sulfenylated AAT1 at Cys192. Mechanistically, thiol reductant DTT treatment or C192S mutation prevented SO2-induced AAT1 sulfenylation and the subsequent inhibition of AAT activity in purified AAT1 protein and primary HUVECs. Our findings reveal, for the first time, a mechanism of auto-regulation of SO2 generation through sulfenylation of AAT1 at Cys192 to suppress AAT activity in vascular endothelial cells. These findings will greatly deepen the understanding of regulatory mechanisms in the cardiovascular homeostasis.

Risk Factors for Orthostatic Hypertension in Children.

OBJECTIVE: To investigate the risk factors for orthostatic hypertension in children. STUDY DESIGN: Eighty children with orthostatic hypertension were enrolled in the group with orthostatic hypertension, and 51 healthy children served as the control group. Demographic characteristics, clinical history, daily water intake, nightly sleep duration, the results of the standing test, and complete blood count were recorded and compared between the 2 groups. The risk factors for pediatric orthostatic hypertension were determined by logistic regression analysis. RESULTS: Body mass index and red blood cell distribution width were higher in the group with orthostatic hypertension than in healthy children, whereas daily water intake and sleep duration were lower. Logistic regression analyses showed that, if a child suffered from overweight, suffered from obesity, had a daily water intake of less than 800 mL, or had a red blood cell distribution width that was increased by 1%, the risk of orthostatic hypertension would be increased by 6.069 times (95% CI, 1.375-26.783; P < .05), 7.482 times (95% CI, 1.835-30.515; P < .01), 4.027 times (95% CI, 1.443-11.241; P < .01), or 4.008 times (95% CI, 1.698-9.461; P < .01), respectively. However, if the sleep duration was increased by 1 hour, the risk of developing orthostatic hypertension would be decreased by 74.3% (95% CI, 54.6%-85.4%, P < .01). CONCLUSIONS: Increased body mass index, inadequate water intake and sleep duration, and elevated red blood cell distribution width were identified as risk factors for pediatric orthostatic hypertension.

Sulfur Dioxide: An Endogenous Protector Against Myocardial Injury.

Sulfur dioxide (SO2) was previously known as a harmful gas in air pollution. Recently, it was reported that SO2 can be endogenously generated in cardiovascular tissues. Many studies have revealed that endogenous SO2 has important physiological and pathophysiological significance and pharmacological potential. As a novel gasotransmitter, SO2 has important regulatory effects on the heart. It has a dose-dependent negative inotropic effect on cardiac function, in which L-type calcium channels are involved. SO2 can also attenuate myocardial injury caused by various harmful stimuli and play an important role in myocardial ischemia-reperfusion injury and myocardial hypertrophy. These effects are thought to be linked to its ability to reduce inflammation and as an antioxidant. In addition, SO2 regulates cardiomyocyte apoptosis and autophagy. Therefore, endogenous SO2 plays an important role in maintaining cardiovascular system homeostasis. In the present review, the literature concerning the metabolism of endogenous SO2, its cardiac toxicological effects and physiological regulatory effects, mechanisms for SO2-mediated myocardial protection and its pharmacological applications are summarized and discussed.

Safety and effect of sildenafil on treating paediatric pulmonary arterial hypertension: a meta-analysis on the randomised controlled trials.

BACKGROUND: Efficacy of sildenafil in treating paediatric pulmonary arterial hypertension is controversial. This systematic review aimed to explore the safety and effect of sildenafil on treating paediatric pulmonary arterial hypertension (PAH) through meta-analysis. METHODS AND RESULTS: In this study, the electronic databases, including the Cochran Library database, EMBASE, and MEDLINE were systemically retrieved to identify the related randomised controlled trials (RCTs). Two reviewers had independently completed study selection, data collection, and assessment of the bias risk. Amongst 938 articles researched according to our retrieval strategy, 15 papers that involved 673 cases had been screened. Relative to control group, the sildenafil group had markedly reduced mortality (RR = 0.25, 95% CI: 0.12-0.51; p < 0.0001), but difference within the mortality was not statistically significant between high- and low-dose sildenafil groups (p = 0.152). Nonetheless, difference of the mean pulmonary arterial pressure between sildenafil as well as control group was of no statistical significance. Differences in the length of hospital stay and the incidences of pulmonary hypertensive crisis between children with PAH and controls were of no statistical significance. However, the summary estimate favoured that sildenafil reduced the duration of mechanical ventilation time, as well as the length of ICU stay and inotropic support. CONCLUSIONS: Sildenafil therapy reduces the mortality of PAH patients, but its effects on the haemodynamic outcomes and other clinical outcomes are still unclear.

Angiotensin II downregulates vascular endothelial cell hydrogen sulfide production by enhancing cystathionine γ-lyase degradation through ROS-activated ubiquitination pathway.

The interactions between vasoactive peptides and gasotransmitters have attracted considerable attention from scientists. However, the impact of angiotensin II (AngII) on the endogenous hydrogen sulfide/cystathionine γ-lyase (H2S/CSE) pathway in vascular endothelial cells remains unclear. In this study, we found, for the first time, that AngII downregulated the endogenous H2S/CSE pathway in a time-dependent manner. Mechanistically, AngII accelerated the degradation of the CSE protein and shortened its half-life in endothelial cells. AngII significantly induced Lys48 (K48)-linked CSE ubiquitination and subsequent CSE degradation but did not affect Lys63 (K63)-linked CSE ubiquitination in vascular endothelial cells. Treatment with the proteasome inhibitor MG132 and mutation of Lys48 to Arg in ubiquitin successfully blunted the inhibitory effects of AngII on the endogenous H2S/CSE pathway in vascular endothelial cells. Furthermore, we found that superoxide anion levels were significantly increased in AngII-treated endothelial cells compared with controls and that the ROS scavenger N-acetyl-l-cysteine (NAC) significantly abolished CSE ubiquitination. Taken together, our data suggested that AngII inhibited endogenous H2S generation through ubiquitination-mediated CSE degradation via the ROS pathway in vascular endothelial cells.

Frequency Domain Indices of Heart Rate Variability are Useful for Differentiating Vasovagal Syncope and Postural Tachycardia Syndrome in Children.

OBJECTIVE: To explore the value of frequency domain indices of heart rate variability (HRV) in the differential diagnosis between pediatric vasovagal syncope and postural tachycardia syndrome (POTS). STUDY DESIGN: Eighty-five patients aged 7-16 years with either vasovagal syncope or POTS were enrolled in the experimental group; 18 healthy children served as controls. Holter electrocardiography was used to detect HRV frequency-domain indices in patients with vasovagal syncope, patients with POTS, and control subjects. The differences in HRV indices were compared between the vasovagal syncope and POTS groups. The receiver operating characteristic (ROC) curve was calculated to analyze the predictive value of HRV for the differential diagnosis between vasovagal syncope and POTS in children. In addition, 37 children aged 7-17 years with either vasovagal syncope or POTS were recruited as an external validation group. RESULTS: The daytime ultra-low frequency (dULF), nighttime ULF (nULF), daytime very low frequency (dVLF), and nighttime VLF (nVLF) were higher in the vasovagal syncope group compared with the POTS group (P < .01 for dULF, dVLF, and nVLF; P < .05 for nULF). The dULF, nULF, dVLF, and nVLF yielded a sensitivity of 73.3%, 71.1%, 68.9%, and 62.2%, respectively, and a specificity of 72.5%, 62.5%, 60.0%, and 60.0%, respectively, to differentiate vasovagal syncope from POTS. The external validation with clinical diagnostic standard showed that a dULF cutoff value of 36.2 ms2 for differentiating POTS from vasovagal syncope yielded a sensitivity of 71.4%, a specificity of 75.0%, and an accuracy of 73.0%. CONCLUSION: dULF may be a useful measure for the differential diagnosis between vasovagal syncope and POTS in adolescents.

Acceleration Index Predicts Efficacy of Orthostatic Training on Vasovagal Syncope in Children.

OBJECTIVE: To explore the value of the acceleration index as a predictor of therapeutic response to orthostatic training in children with vasovagal syncope (VVS). STUDY DESIGN: Thirty-three children with VVS were recruited and treated with orthostatic training. The therapeutic response of each patient was evaluated after 3 months of treatment. A Pearson correlation was calculated between the acceleration index and the severity of VVS. The value of the acceleration index in predicting the therapeutic response to orthostatic training was assessed by analysis of the receiver operating characteristic curve. RESULTS: Among the 33 children with VVS, 20 were found to be responders and the remaining were nonresponders. The mean acceleration index was significantly lower in responders compared with nonresponders (21.10 ± 6.61 vs 31.36 ± 9.00; P = .001) and it was negatively correlated with positive response time in the head-up tilt test, with systolic blood pressure and with diastolic blood pressure at positive response time in the head-up tilt test (P < .05). The receiver operating characteristic curve for the predictive value of the acceleration index showed that the area under the curve was 0.827 (95% CI, 0.676-0.978; P = .002), and a cutoff value of the acceleration index of 26.77 yielded a sensitivity of 85.0% and a specificity of 69.2%. CONCLUSIONS: The acceleration index may be useful for predicting the efficacy of orthostatic training on VVS in children.

Endogenous hydrogen sulfide sulfhydrates IKKß at cysteine 179 to control pulmonary artery endothelial cell inflammation.

BACKGROUND: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. METHODS: Purified recombinant human inhibitor of κB kinase subunit ß (IKKß) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. RESULTS: We showed that hydrogen sulfide (H2S) inhibited IKKß activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKß activity directly via sulfhydrating IKKß at cysteinyl residue 179 (C179) in purified recombinant IKKß protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKß inactivation. Furthermore, to demonstrate the significance of IKKß sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKß. In purified IKKß protein, C179S mutation of IKKß abolished H2S-induced IKKß sulfhydration and the subsequent IKKß inactivation. In human PAECs, C179S mutation of IKKß blocked H2S-inhibited IKKß activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKß abolished the inhibitory effect of H2S on IKKß activation and pulmonary vascular inflammation and remodeling. CONCLUSION: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKß via sulfhydrating IKKß at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.

Recombinant Human Erythropoietin Protects Against Hippocampal Damage in Developing Rats with Seizures by Modulating Autophagy via the S6 Protein in a Time-Dependent Manner.

Epilepsy is among the most common neurological disorders. Recurrent seizures result in neuronal death, cognitive deficits and intellectual disabilities in children. Currently, recombinant human erythropoietin (rhEPO) is considered to play a neuroprotective role in nervous system disorders. However, the precise mechanisms through which rhEPO modulates epilepsy remain unknown. Based on results from numerous studies, we hypothesized that rhEPO protects against hippocampal damage in developing rats with seizures probably by modulating autophagy via the ribosomal protein S6 (S6) in a time-dependent manner. First, we observed that rats with recurrent seizures displayed neuronal loss in the hippocampal CA1 region. Second, rhEPO injection reduced neuronal loss and decreased the number of apoptotic cells in the hippocampal CA1 region. Moreover, rhEPO increased the Bcl-2 protein expression levels and decreased the ratio of cleaved caspase-3/caspase-3 in the hippocampus. Finally, rhEPO modulated autophagy in the hippocampus in a time-dependent manner, probably via the S6 protein. In summary, rhEPO protects against hippocampal damage in developing rats with seizures by modulating autophagy in a time-dependent manner, probably via the S6 protein. Consequently, rhEPO is a likely drug candidate that is capable of attenuating brain injury.

Head-up tilt test provokes dynamic alterations in total peripheral resistance and cardiac output in children with vasovagal syncope.

AIM: This study examined the total peripheral vascular resistance (TPVR) and cardiac output changes due to the head-up tilt test (HUTT) in children with vasovagal syncope (VVS). METHODS: From December 2013 to January 2016, we recruited 77 children diagnosed with VVS group at Peking University First Hospital, China, and 28 children without VVS provided the control group. Heart rate, blood pressure, TPVR, cardiac output and baroreflex sensitivity were monitored during the HUTT. RESULTS: In the supine position, TPVR and baroreflex sensitivity were higher in the patients with VVS than the controls, but cardiac output did not differ between the two groups. There were obvious increases in the VVS patients from TPVR in the supine position to the prepositive response period (p < 0.05), then the positive response period (p < 0.01). However, we noted the opposite trend in cardiac output, from the supine position to the prepositive response period (p < 0.01) then the positive response period (p < 0.01). CONCLUSION: During HUTT, children with VVS demonstrated increases in TPVR but decreases in cardiac output, during the transition from the supine position to the positive response. This response might be involved in the pathogenesis of VVS.

Prediction of Therapeutic Response to Cyclooxygenase Inhibitors in Preterm Infants with Patent Ductus Arteriosus.

Patent ductus arteriosus (PDA) is a morbid condition commonly seen in premature infants. Cyclooxygenase (COX) inhibitors, such as indomethacin and ibuprofen, are often used for the treatment of PDA in preterm infants, and they work by reducing the production of prostaglandin. However, as observed in clinical practice, not all PDAs in preterm infants can be closed using COX inhibitors. Some studies have demonstrated that gestational age, birth weight, B-type natriuretic peptide (BNP), and ductal diameter can predict the therapeutic responsiveness to COX inhibitors. This paper reviews the factors that can predict successful closure of the PDA in preterm infants using indomethacin or ibuprofen and presents new opinions and recent findings on this topic, including the predictive roles of intrauterine growth restriction, timing of the treatment, and the importance of platelet count and arterial pH. We also discuss the prospects for future studies to improve the individualized therapy of PDA in premature neonates.

Left Ventricular Ejection Fraction and Fractional Shortening are Useful for the Prediction of the Therapeutic Response to Metoprolol in Children with Vasovagal Syncope.

The objective of this manuscript was to explore if left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) could predict the efficacy of metoprolol therapy on vasovagal syncope (VVS) in children. Forty-nine children, including 30 with VVS and 19 gender- and age-matched healthy controls, were included in the study. Metoprolol was prescribed to the VVS subjects. The clinical data were obtained during follow-up at 2 and 6 months. The results showed that LVEF and LVFS of responders were significantly higher than those of non-responders both at the 2-month follow-up (LVEF: 72.5 ± 3.2% vs. 64.6 ± 3.4%; LVFS: 40.9 ± 2.3% vs. 34.9 ± 2.9%), and at the 6-month follow-up (LVEF: 72.8 ± 2.8% vs. 65.5 ± 4.6%; LVFS: 41.1 ± 1.9% vs. 35.8 ± 3.6%). The receiver operating characteristic curve (ROC) analysis demonstrated that 70.5% as a cutoff value of baseline LVEF yielded a sensitivity of 80% and a specificity of 100% in predicting the therapeutic effectiveness of metoprolol at 2 months. For baseline LVFS, 38.5% as a cutoff value yielded a sensitivity of 90% and a specificity of 90%. At the 6-month follow-up, the ROC analysis demonstrated that 70.5% as a cutoff value of baseline LVEF yielded a sensitivity of 81.3% and a specificity of 88.9% in the prediction of metoprolol efficacy. For baseline LVFS, 37.5% as a cutoff value yielded a sensitivity of 93.8% and a specificity of 66.7%. In conclusion, baseline LVEF and LVFS might be useful predictors of the efficacy of ß-blocker therapy on VVS in children.

H2S inhibits pulmonary arterial endothelial cell inflammation in rats with monocrotaline-induced pulmonary hypertension.

This study aimed to determine whether hydrogen sulfide (H2S) inhibits pulmonary arterial endothelial inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension and its possible mechanisms. Twenty-four male Wistar rats were divided randomly into control, MCT, and MCT+H2S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+H2S, and H2S. Pulmonary artery pressure was determined using a right cardiac catheterization procedure 3 weeks after MCT administration. Pulmonary vascular morphological changes and inflammatory infiltration were measured. Endogenous H2S levels, cystathionine-γ-lyase (CSE) expression, and inflammatory cytokines were determined both in vivo and in vitro. In addition, phosphorylation of NF-κB p65 and IκBα was detected by western blotting, and NF-κB p65 nuclear translocation, as well as its DNA-binding activity, was determined. Pulmonary hypertension and vascular remolding developed 3 wks after MCT administration, with elevated lung tissue inflammatory infiltration and cytokine level associated with activation of the NF-κB pathway, both in vivo and in vitro. However, the endogenous H2S/CSE pathway was downregulated in MCT rats. By contrast, an H2S donor markedly reduced pulmonary artery pressure, pulmonary vascular structural remolding, and increased lung inflammatory infiltration and cytokine levels of MCT-treated rats. Meanwhile, H2S reversed the activation of the NF-κB pathway successfully. The downregulated pulmonary arterial endothelial H2S/CSE pathway is involved in the pulmonary inflammatory response in MCT-treated pulmonary hypertensive rats. H2S attenuated endothelial inflammation by inhibiting the NF-κB pathway.

Hemocytometric Measures Predict the Efficacy of Oral Rehydration for Children with Postural Tachycardia Syndrome.

OBJECTIVE: To explore whether hemocytometric measures could be qualified predictors for the effect of oral rehydration salts (ORS) in children with postural tachycardia syndrome (POTS). STUDY DESIGN: Thirty-five children with POTS and 29 healthy children were enrolled. General information, hemodynamic status, and baseline hemocytometric variables were collected. Children with POTS received ORS therapy and were followed up for 3 months. The independent risk factors of developing POTS were explored. A receiver-operating characteristic curve was used to evaluate predictive value of hemocytometric variables for therapeutic effectiveness of ORS therapy. RESULTS: Children with POTS had larger mean corpuscular volume (MCV) and lower mean corpuscular hemoglobin concentration (MCHC) values than controls (P < .05). The baseline MCV values positively correlated with heart rate elevation from supine to upright (r = 0.294, P < .05). Both larger MCV and lower MCHC values were independent risk factors of developing POTS (for MCV, P < .05, OR 1.222; for MCHC, P < .05, OR 0.936). In children with POTS, responders to ORS had baseline lower MCV and higher MCHC than nonresponders (P < .05). The receiver-operating characteristic curve for the predictive value of MCHC showed that area under the curve was 0.73. CONCLUSIONS: MCHC values could be used to predict the effectiveness of ORS for treating POTS in children.