Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy / 中华医学杂志(英文版)

BACKGROUND@#Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.@*METHODS@#This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of  0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013).@*CONCLUSIONS@#Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.

Body mass index is a promising predictor of response to oral rehydration saline in children with vasovagal syncope / 中华医学杂志(英文版)

BACKGROUND@#Vasovagal syncope (VVS) greatly impairs quality of life. The therapeutic efficacy of oral rehydration saline (ORS) for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease. Body mass index (BMI) was demonstrated to reflect blood volume to a certain extent. Therefore, the present study explored the capability of BMI to predict the therapeutic response of children with VVS to ORS treatment.@*METHODS@#Seventy-four children with VVS who visited the Syncope Unit of Pediatrics at Peking University First Hospital from November 2010 to June 2019 receiving ORS treatment were enrolled for this retrospective case-control study. A comparison of demographic, clinical, and hemodynamic characteristics was performed between responders and non-responders. The correlation between baseline BMI and response time was analyzed. To determine the value of baseline BMI in predicting the therapeutic efficacy of ORS in children with VVS, a receiver operating characteristic curve analysis was performed.@*RESULTS@#Fifty-two children were identified as responders, and the remaining 22 children were identified as non-responders. The baseline BMI of the responders was much lower than that of the non-responders (16.4 [15.5, 17.8] kg/m2vs. 20.7 ±e6 kg/m2, P < 0.001), and baseline BMI was positively correlated with response time in the head-up tilt test after adjusting for sex (r = 0.256, 95% confidence interval [CI]: 0.067-0.439, P = 0.029). The area under the receiver operating characteristic curve of baseline BMI was 0.818 (95% CI: 0.704-0.932, P < 0.001), and an optimal cut-off value of 18.9 kg/m2 yielded a sensitivity of 83% and a specificity of 73% to predict the efficacy of ORS in VVS.@*CONCLUSION@#Prior to treatment, baseline BMI is a promising predictor of response to ORS in children with VVS.

Gut microbiota analysis and its significance in vasovagal syncope in children / 中华医学杂志(英文版)

BACKGROUND@#Vasovagal syncope (VVS) is common in children and greatly affect both physical and mental health. But the mechanisms have not been completely explained. This study was designed to analyze the gut microbiota in children with VVS and explore its clinical significance.@*METHODS@#Fecal samples from 20 VVS children and 20 matched controls were collected, and the microbiota were analyzed by 16S rRNA gene sequencing. The diversity and microbiota compositions of the VVS cases and controls were compared with the independent sample t test or Mann-Whitney U test. The correlation between the predominant bacteria and clinical symptoms was analyzed using Pearson or Spearman correlation test.@*RESULTS@#No significant differences in diversity were evident between VVS and controls (P > 0.05). At the family level, the relative abundance of Ruminococcaceae was significantly higher in VVS children than in controls (median [Q1, Q3]: 22.10% [16.89%, 27.36%] vs. 13.92% [10.31%, 20.18%], Z = -2.40, P  4, P < 0.05). The relative abundance of Ruminococcaceae in VVS patients was positively correlated with the frequency of syncope (r = 0.616, P < 0.01). In terms of its correlation with hemodynamics, we showed that relative abundance of Ruminococcaceae was negatively correlated with the systolic and diastolic pressure reduction at the positive response in head-up tilt test (HUTT; r = -0.489 and -0.448, all P < 0.05), but was positively correlated with the mean pressure drop and decline rate (r = 0.489 and 0.467, all P < 0.05) as well as diastolic pressure drop and decline rate at the HUTT positive response (r = 0.579 and 0.589, all P < 0.01) in VVS patients.@*CONCLUSION@#Ruminococcaceae was the predominant gut bacteria and was associated with the clinical symptoms and hemodynamics of VVS, suggesting that gut microbiota might be involved in the development of VVS.

Hemodynamic changes in standing-up test of children and adolescents with postural tachycardia syndrome / 北京大学学报(医学版)

OBJECTIVE@#To explore the hemodynamic changes in standing-up test of children and adolescents with postural tachycardia syndrome (POTS) and to compare hemodynamic parameters of POTS patients with decreased cardiac index (CI) and those with not-decreased CI.@*METHODS@#A retrospective study was conducted to show the trends of CI, total peripheral vascular resistance index (TPVRI), heart rate and blood pressure in standing-up test of 26 POTS patients and 12 healthy controls, and to compare them between the two groups. The POTS patients were divided into two groups based on CI decreasing or not in standing-up test, namely decreased CI group (14 cases) and not-decreased CI group (12 cases). The trends of the above mentioned hemodynamic parameters in standing-up test were observed and compared between decreased CI group and not-decreased CI group.@*RESULTS@#In standing-up test for all the POTS patients, CI (F=6.936, P=0.001) and systolic blood pressure (F=6.049, P<0.001) both decreased significantly, and heart rate increased obviously (F=113.926, P<0.001). However, TPVRI (F=2.031, P=0.138) and diastolic blood pressure (F=2.018, P=0.113) had no significant changes. For healthy controls, CI (F=3.646, P=0.016), heart rate (F=43.970, P<0.001), systolic blood pressure (F=4.043, P=0.020) and diastolic blood pressure (F=8.627, P<0.001) all increased significantly in standing-up test. TPVRI (F=1.688, P=0.190) did not change obviously. The changing trends of CI (F=6.221, P=0.001), heart rate (F=6.203, P<0.001) and systolic blood pressure (F=7.946, P<0.001) over time were significantly different between the patients and healthy controls, however, no difference was found in TPVRI and diastolic blood pressure (P > 0.05). Among the POTS patients, CI was significantly different between decreased CI group and not-decreased CI group (F=14.723, P<0.001). Systolic blood pressure of the former decreased obviously (F=8.010, P<0.001), but it did not change obviously in the latter (F=0.612, P=0.639). Furthermore, none of the changes of TPVRI, heart rate and diastolic blood pressure in standing-up test were significantly different between the two groups (P > 0.05). Age was an independent factor for decreased CI patients (P=0.013, OR=2.233; 95% CI, 1.183 to 4.216).@*CONCLUSION@#POTS patients experience vital hemodynamic changes in standing-up test, part of them suffering from decreased CI, but others from not-decreased CI. Age is an independent factor for patients suffering from decreased CI.

Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration / 中华医学杂志(英文版)

<p><b>Background</b>Myocardial fibrosis is an important pathological change in many heart diseases, but its pathogenesis is very complex and has not yet been fully elucidated. The study was designed to examine whether endogenous sulfur dioxide (SO) is a novel myocardial fibroblast proliferation and migration inhibitor.</p><p><b>Methods</b>Primary rat myocardial fibroblasts were isolated and transfected with aspartate aminotransferase (AAT1 and AAT2) knockdown lentivirus or empty lentivirus. SO content in the supernatant was determined with high-performance liquid chromatography, and the expressions of AAT1, AAT2, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated protein kinase (p-ERK), and total ERK (T-ERK) in the cells were detected. Cell migration was detected by wound healing test. Independent sample t-test (for two groups) and one-way analysis of variance (three or more groups) were used to analyze the results.</p><p><b>Results</b>Both AAT1 and AAT2 knockdown significantly reduced SOlevels (F = 31.46, P < 0.01) and AAT1/2 protein expression (AAT1, t = 12.67, P < 0.01; AAT2, t = 9.61, P < 0.01), but increased PCNA expression and Cell Counting Kit-8 (CCK-8) activity as well as the migration in rat primary myocardial fibroblasts (P < 0.01). Supplementation of SOrather than pyruvate significantly inhibited the increase in proliferation and migration caused by AAT knockdown (P < 0.01). Mechanistically, the ratio of p-ERK to T-ERK was significantly increased in the AAT1/2 knockdown groups compared with that in the empty lentivirus group (AAT1, t = -7.36, P < 0.01; AAT2, t = -10.97, P < 0.01). Whereas PD98059, an inhibitor of ERK activation, successfully blocked AAT knockdown-induced PCNA upregulation (F = 74.01, P > 0.05), CCK-8 activation (F = 50.14, P > 0.05), and migration augmentation in myocardial fibroblasts (24 h, F = 37.08, P > 0.05; 48 h, F = 58.60, P > 0.05).</p><p><b>Conclusion</b>Endogenous SOmight be a novel myocardial fibroblast proliferation and migration inhibitor via inhibiting the ERK signaling pathway.</p>

Hydrogen Sulfide Regulating Myocardial Structure and Function by Targeting Cardiomyocyte Autophagy / 中华医学杂志(英文版)

<p><b>Objective</b>Hydrogen sulfide (HS), a gaseous signal molecule, plays a crucial role in many pathophysiologic processes in the cardiovascular system. Autophagy has been shown to participate in the occurrence of many cardiac diseases. Increasing evidences indicated that HS regulates myocardial structure and function in association with the altered autophagy and plays a "switcher" role in the autophagy of myocardial diseases. The aim of this review was to summarize these insights and provide the experimental evidence that HS targets cardiomyocyte autophagy to regulate cardiovascular function.</p><p><b>Data Sources</b>This review was based on data in articles published in the PubMed databases up to October 30, 2017, with the following keywords: "hydrogen sulfide," "autophagy," and "cardiovascular diseases."</p><p><b>Study Selection</b>Original articles and critical reviews on HS and autophagy were selected for this review.</p><p><b>Results</b>When autophagy plays an adaptive role in the pathogenesis of diseases, HS restores autophagy; otherwise, when autophagy plays a detrimental role, HS downregulates autophagy to exert a cardioprotective function. For example, HS has beneficial effects by regulating autophagy in myocardial ischemia/reperfusion and plays a protective role by inhibiting autophagy during the operation of cardioplegia and cardiopulmonary bypass. HS postpones cardiac aging associated with the upregulation of autophagy but improves the left ventricular function of smoking rats by lowering autophagy.</p><p><b>Conclusions</b>HS exerts cardiovascular protection by regulating autophagy. Cardiovascular autophagy would likely become a potential target of HS therapy for cardiovascular diseases.</p>

Increased Endogenous Sulfur Dioxide Involved in the Pathogenesis of Postural Tachycardia Syndrome in Children: A Case-Control Study / 中华医学杂志(英文版)

<p><b>Background</b>The pathogenesis of postural tachycardia syndrome (POTS) remains unclear. This study aimed to explore the changes and significance of sulfur dioxide (SO) in patients with POTS.</p><p><b>Methods</b>The study included 31 children with POTS and 27 healthy children from Peking University First Hospital between December 2013 and October 2015. A detailed medical history, physical examination results, and demographic characteristics were collected. Hemodynamics was recorded and the plasma SOwas determined.</p><p><b>Results</b>The plasma SOwas significantly higher in POTS children compared to healthy children (64.0 ± 20.8 μmol/L vs. 27.2 ± 9.6 μmol/L, respectively, P < 0.05). The symptom scores in POTS were positively correlated with plasma SOlevels (r = 0.398, P < 0.05). In all the study participants, the maximum heart rate (HR) was positively correlated with plasma levels of SO(r = 0.679, P < 0.01). The change in systolic blood pressure from the supine to upright (ΔSBP) in POTS group was smaller than that in the control group (P < 0.05). The ΔSBP was negatively correlated with baseline plasma SOlevels in all participants (r = -0.28, P < 0.05). In the control group, ΔSBP was positively correlated with the plasma levels of SO(r = 0.487, P < 0.01). The change in HR from the supine to upright in POTS was obvious compared to that of the control group. The area under curve was 0.967 (95% confidence interval: 0.928-1.000), and the cutoff value of plasma SOlevel >38.17 μmol/L yielded a sensitivity of 90.3% and a specificity of 92.6% for predicting the diagnosis of POTS.</p><p><b>Conclusions</b>Increased endogenous SOlevels might be involved in the pathogenesis of POTS.</p>

Plasma Neuropeptide Y Levels in Vasovagal Syncope in Children / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Vasovagal syncope (VVS) is the most common cause of syncope in children. Neuropeptide Y (NPY) plays an important role in the regulation of blood pressure (BP), as well as myocardial contractility. This study aimed to explore the role of plasma NPY in VVS in children.</p><p><b>METHODS</b>Fifty-six children who were diagnosed with VVS (VVS group) using head-up tilt test (HUT) and 31 healthy children who were selected as controls (control group) were enrolled. Plasma NPY concentrations were detected. The independent t-test was used to compare the data of the VVS group with those of the control group. The changes in plasma NPY levels in the VVS group during the HUT, as well as hemodynamic parameters, such as heart rate (HR), BP, total peripheral vascular resistance (TPVR), and cardiac output (CO), were evaluated using the paired t-test. Furthermore, the correlations between plasma NPY levels and hemodynamic parameters were analyzed using bivariate correlation analysis.</p><p><b>RESULTS</b>The BP, HR, and plasma NPY (0.34 ± 0.12 pg/ml vs. 0.46 ± 0.13 pg/ml) levels in the supine position were statistically low in the VVS group compared to levels in the control group (all P < 0.05). Plasma NPY levels were positively correlated with the HR (Pearson, R = 0.395, P < 0.001) and diastolic BP (Pearson, R = 0.311, P = 0.003) when patients were in the supine position. When patients in the VVS group were in the supine position, elevated TPVR (4.6 ± 3.7 mmHg·min-1·L-1 vs. 2.5 ± 1.0 mmHg·min-1·L-1, respectively, P < 0.001; 1 mmHg = 0.133 kPa) and reduced CO (1.0 ± 0.7 L/min vs. 2.4 ± 1.3 L/min, respectively, P < 0.001) were observed in the positive-response period compared with baseline values. The plasma NPY levels were positively correlated with TPVR (Spearman, R = 0.294, P = 0.028) but negatively correlated with CO in the positive-response period during HUT (Spearman, R = -0.318, P = 0.017).</p><p><b>CONCLUSIONS</b>Plasma NPY may contribute to the pathogenesis of VVS by increasing the TPVR and decreasing the CO during orthostatic regulation.</p>

Vitamin D and Cardiovascular Risk in Children / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Vitamin D is a group of fat-soluble molecules that are structurally similar to steroids. Emerging data have led to the hypothesis that Vitamin D plays a role in the regulation of many physiological processes beyond calcium and phosphorus homeostasis. With this review, we aimed to summarize the changes in Vitamin D levels in children with cardiovascular diseases based on the literature. In addition, we also reviewed the potential mechanisms underlying cardiovascular diseases associated with Vitamin D deficiency or insufficiency.</p><p><b>DATA SOURCES</b>The articles in English were searched from PubMed (1968-2016) and EMBASE (1991-2016), with the keywords of "Vitamin D AND cardiovascular diseases" and "Vitamin D AND children."</p><p><b>STUDY SELECTION</b>Original articles and critical reviews about Vitamin D and cardiovascular risk in children were selected for review. Researches focused on adults were excluded.</p><p><b>RESULTS</b>Studies have shown that several pediatric cardiovascular diseases may be associated with Vitamin D deficiency or insufficiency, including hypertension, orthostatic intolerance, and Kawasaki disease.</p><p><b>CONCLUSIONS</b>Vitamin D may play a role in the regulation of the cardiovascular system. Further investigation would hopefully disclose the usefulness of Vitamin D as a biomarker for cardiovascular diseases in children.</p>

Sulfur Dioxide Inhibits Extracellular Signal-regulated Kinase Signaling to Attenuate Vascular Smooth Muscle Cell Proliferation in Angiotensin II-induced Hypertensive Mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Clarifying the mechanisms underlying vascular smooth muscle cell (VSMC) proliferation is important for the prevention and treatment of vascular remodeling and the reverse of hyperplastic lesions. Previous research has shown that the gaseous signaling molecule sulfur dioxide (SO2) inhibits VSMC proliferation, but the mechanism for the inhibition of the angiotensin II (AngII)-induced VSMC proliferation by SO2has not been fully elucidated. This study was designed to investigate if SO2inhibited VSMC proliferation in mice with hypertension induced by AngII.</p><p><b>METHODS</b>Thirty-six male C57 mice were randomly divided into control, AngII, and AngII + SO2groups. Mice in AngII group and AngII + SO2group received a capsule-type AngII pump implanted under the skin of the back at a slow-release dose of 1000 ng·kg-1·min-1. In addition, mice in AngII + SO2received intraperitoneal injections of SO2donor. Arterial blood pressure of tail artery was determined. The thickness of the aorta was measured by elastic fiber staining, and proliferating cell nuclear antigen (PCNA) and phosphorylated-extracellular signal-regulated kinase (P-ERK) were detected in aortic tissues. The concentration of SO2 in serum and aortic tissue homogenate supernatant was measured using high-performance liquid chromatography with fluorescence determination. In the in vitro study, VSMC of A7R5 cell lines was divided into six groups: control, AngII, AngII + SO2, PD98059 (an inhibitor of ERK phosphorylation), AngII + PD98059, and AngII + SO2 + PD98059. Expression of PCNA, ERK, and P-ERK was determined by Western blotting.</p><p><b>RESULTS</b>In animal experiment, compared with the control group, AngII markedly increased blood pressure (P < 0.01) and thickened the aortic wall in mice (P < 0.05) with an increase in the expression of PCNA (P < 0.05). SO2, however, reduced the systemic hypertension and the wall thickness induced by AngII (P < 0.05). It inhibited the increased expression of PCNA and P-ERK induced by AngII (P < 0.05). In cell experiment, PD98059, an ERK phosphorylation inhibitor, blocked the inhibitory effect of SO2on VSMC proliferation (P < 0.05).</p><p><b>CONCLUSIONS</b>ERK signaling is involved in the mechanisms by which SO2inhibits VSMC proliferation in AngII-induced hypertensive mice via ERK signaling.</p>

Pathogenesis and Individualized Treatment for Postural Tachycardia Syndrome in Children / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Postural tachycardia syndrome (POTS) is one of the major causes of orthostatic intolerance in children. We systematically reviewed the pathogenesis and the progress of individualized treatment for POTS in children.</p><p><b>DATA SOURCES</b>The data analyzed in this review are mainly from articles included in PubMed and EMBASE.</p><p><b>STUDY SELECTION</b>The original articles and critical reviews about POTS were selected for this review.</p><p><b>RESULTS</b>Studies have shown that POTS might be related to several factors including hypovolemia, high catecholamine status, abnormal local vascular tension, and decreased skeletal muscle pump activity. In addition to exercise training, the first-line treatments mainly include oral rehydration salts, beta-adrenoreceptor blockers, and alpha-adrenoreceptor agonists. However, reports about the effectiveness of various treatments are diverse. By analyzing the patient's physiological indexes and biomarkers before the treatment, the efficacy of medication could be well predicted.</p><p><b>CONCLUSIONS</b>The pathogenesis of POTS is multifactorial, including hypovolemia, abnormal catecholamine state, and vascular dysfunction. Biomarker-directed individualized treatment is an important strategy for the management of POTS children.</p>

Effects of hydrogen sulfide donor on production of adrenomedullin and atrial natriuretic peptide in rats with atherosclerosis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Endogenous hydrogen sulfide (H2S), a novel gasotransmitter in cardiovascular regulation, plays an important protective role in the development and progression of atherosclerosis (AS). This study was designed to explore the effects of H2S donor on the production of adrenomedullin (ADM) and atrial natriuretic peptide (ANP) in AS rats.</p><p><b>METHODS</b>Male Sprague-Dawley rats were randomly divided into control group (n=10), AS group (n=10), and AS+NaHS group (n=10). Rats in the AS and AS+NaHS groups were given 3-day intraperitoneal injections of vitamin D3 and 8-week high-fat diet to induce AS, and the rats in the AS+NaHS group were intraperitoneally injected with H2S donor NaHS. Oil red O staining was applied to detect changes in the areas of the atherosclerotic plaques in the aortic root and the coronary artery; sulfide-sensitive electrode method was used to measure the plasma concentration of H2S. ADM and ANP levels in plasma were determined by radioimmunoassay.</p><p><b>RESULTS</b>Compared with the control group, marked atherosclerotic plaques were observed in the aortic root and the coronary artery in AS rats. Moreover, plasma H2S level decreased significantly, ADM level increased, and ANP level decreased significantly in AS rats (P<0.01). However, after the treatment with H2S donor NaHS for 8 weeks, the above changes in AS rats were reversed, demonstrated by significantly reduced areas of the atherosclerotic plaques in both the aortic root and the coronary artery, significantly increased plasma H2S level, significantly decreased plasma ADM level, and significantly increased plasma ANP level (P<0.01).</p><p><b>CONCLUSIONS</b>H2S plays an important regulatory effect on vasoactive peptides ADM and ANP in AS rats.</p>

Clinical analysis and follow-up study of cardiavascular system involvement in 10 children with methylmalonic aciduria combined with hyperhomocysteinemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical features and treatment outcomes of cardiovascular system involvement in children with methylmalonic aciduria combined with hyperhomocysteinemia (MMACHC).</p><p><b>METHODS</b>The clinical data of 10 children with methylmalonic aciduria combined with hyperhomocysteinemia and who had cardiovascular system involvement were retrospectively analyzed and the treatment outcomes were followed up.</p><p><b>RESULTS</b>In the 10 patients, there were 4 cases with initial presentations of cardiovascular system symptoms such as shortness of breath and dyspnea, 3 cases with urinary tract symptoms such as edema, hematuria and proteinuria, and 3 cases with nervous system symptoms such as developmental retardation and convulsions. The 10 patients had different types and severity of cardiovascular injuries. After 3 months to 8 years of follow-up, the congenital heart defects resolved naturally in 2 cases, and the patient with arrhythmia had no obvious changes. In 5 cases of hypertension, blood pressures recovered to normal in 3 cases, and 1 case was lost to follow-up. In 5 patients with pulmonary hypertension, 2 died, 2 recovered, and 1 case had mildly elevated pulmonary artery pressure. Seven patients underwent MMACHC gene testing, and 5 showed c.80A>G mutations.</p><p><b>CONCLUSIONS</b>Metabolic disease should be taken into account for the children with unexplained pulmonary hypertension and hypertension with the onset of the shortness of breath and dyspnea. The severity of cardiovascular system involvement might be one of the most important factors affecting the prognosis of children with MMACHC. Cardiavascular system involvement of the patients may be related to MMACHC c.80A>G mutations.</p>

Adrenomedullin alleviates collagen accumulation in pulmonary arteries of rats with hypoxic pulmonary hypertension / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the effect of adrenomedullin (ADM) on the pulmonary vascular collagen metabolism in hypoxic rats in order to study the effect of ADM on chronic hypoxic pulmonary vascular structural remodeling and its possible mechanism.</p><p><b>METHODS</b>Nineteen male Wistar rats were randomly divided into three groups: normal control (n=6), hypoxia (n=7) and ADM-treated hypoxia (n=6). ADM was subcutaneously administered into rats of the ADM-treated hypoxia group by mini-osmotic pump (300 ng/h) for two weeks. After two weeks of hypoxic challenge, mean pulmonary arterial pressure (mPAP) was evaluated using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass[RV/ (LV+S)] was measured. The changes of pulmonary vascular microstructure were observed. Meanwhile, the expression levels of collagen I, collagen III and transforming growth factor (TGF)-β in pulmonary arteries were detected by immunohistochemical assay.</p><p><b>RESULTS</b>mPAP and RV/(LV+S) increased significantly in the hypoxia group compared with normal controls (P<0.01). The muscularization of small pulmonary vessels and the relative medial thickness of pulmonary arteries increased obviously in the hypoxia group compared with those in the normal control group (P<0.01). Meanwhile, the expression levels of collagen I, collagen III and TGF-β of pulmonary arteries in the hypoxia group increased markedly compared with those in the normal control group. However, mPAP and RV/(LV+S) were significantly reduced in the ADM-treated hypoxia group compared with those in the hypoxia group (P<0.01). ADM ameliorated pulmonary vascular structural remodeling of hypoxic rats, with a decrease in the expression of collagen I, collagen III and TGF-β of pulmonary arteries.</p><p><b>CONCLUSIONS</b>ADM might play a regulatory role in the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular remodeling, through inhibiting the expression of TGF-β and alleviating the collagen accumulation of pulmonary arteries.</p>

Clinical analysis of orthostatic hypertension in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of orthostatic hypertension (OHT) in children.</p><p><b>METHOD</b>A total of 96 children with OHT who met the diagnostic criteria and clinical manifestations were recruited in the Department of Pediatrics, Peking University First Hospital. Age and sex distributions were observed. The duration of disease, the frequencies of symptoms and the predisposing factors were recorded. The hemodynamic changes from supine to up-right positions were also analyzed.</p><p><b>RESULT</b>There were 50 boys and 46 girls in the study group. The mean age was (11.8 ± 2.7) years. Thirty-two children were from 6 to 10 years old, accounting for 33.3% of all subjects, while 64 patients were from 11 to 17 years old, accounting for 66.7%. Durations of symptoms of OHT were less than 1 month in 22.9% children, from 1 month to 1 year in 51.1% children and longer than 1 year in 26.0% children. The most common clinical manifestations were syncope and dizziness. The incidence of them was 70.8% and 46.9%, respectively. Other clinical manifestations included transitional amaurosis, nausea and/or vomiting, pallor and so on. These clinical manifestations often occurred on position change (24.0%) and long-time standing (57.3%) in children. Other predisposing factors included exercise, emotion changes and fuggy environment. The baseline systolic and diastolic blood pressures were (103 ± 8) mm Hg (1 mm Hg = 0.133 kPa) and (59 ± 6) mm Hg, respectively, the up-right systolic and diastolic blood pressure at 3 min were (113 ± 8) mm Hg and (73 ± 6) mm Hg and the differences were significant (t = 27.674, P < 0.01; t = 17.936, P < 0.01). The baseline heart rate in supine position was (81 ± 11) bpm and the maximum heart rate in up-right position was (113 ± 12) bpm (t = 33.092, P < 0.01).</p><p><b>CONCLUSION</b>OHT is commonly seen in puberty of children. The chief complaints are syncope and dizziness. They were mostly induced by position change and long-time standing. Blood pressure was significantly increased from supine to up-right position.</p>

Modified methylene blue method for measurement of hydrogen sulfide level in plasma / 生理学报

In past decade, hydrogen sulfide (H₂S) as a novel gasotransmitter, covered many fields in biological and medical research. However, there is no effective, convenient and high-throughput method for determination of circulatory H₂S until now. Here, we aim to develop an easy method for measurement of circulatory H₂S by modified methylene blue method. In the present study, we added Zn²⁺ to plasma sample to deposit H₂S, HS⁻ and S²⁻, as well as plasma protein, then used NaOH to re-dissolve plasma protein. ZnS deposition was re-dissolved by the addition of N, N-dimethyl-p-phenylenediamine, and the remnant protein was deposited by trichloroacetic acid. After centrifugation, ferriammonium sulfate was added to the supernatant fluid to generate methylene blue, which was analyzed by spectrophotometer at 665 nm. Using the present method, we found that most ions including sulfate and thiosulfate did not affect detection of H₂S concentration, but albumin (physiological concentration) reduced the detection value, which suggested the binding of serum albumin and a certain amount of H₂S. The relative recovery ratio of present method is 81.9%, which implies that the method is relative accurate for the determination of H₂S concentration in plasma or serum. H₂S levels of frozen plasma samples from 65 healthy volunteers detected by the present method were (13.93 ± 4.98) µmol/L. There was no obvious difference between the detection values of fresh and frozen samples from the same SD rats. These results suggest the modified methylene blue assay is stable, sensitive, convenient and high-throughput. The method can be used to analyze the circulatory H₂S in clinical and basic research.

A modified Calgary syncope syndrome score in the differential diagnosis between cardiac syncope and vasovagal syncope / 中华儿科杂志

<p><b>OBJECTIVE</b>This study aimed at analyzing the usefulness of a modified Calgary Syncope Syndrome Score in the differential diagnosis between cardiac syncope (CS) and vasovagal syncope (VVS) in children through a large sample clinical study.</p><p><b>METHOD</b>Totally 189 children [112 males, 77 females, aged 2 - 18 yrs, mean age (12.4 ± 3.1) yrs] with CS and VVS who were at the syncope clinic or admitted to the Department of Pediatrics, Peking University First Hospital from August 2002 to April 2011 were included in the study. The diagnosis was analyzed by a modified Calgary Syncope Syndrome Score and receiver operating characteristic (ROC) curve was used to explore the predictive value of different Calgary Syncope Syndrome Scores in differential diagnosis between CS and VVS.</p><p><b>RESULT</b>There were significant differences in the score between CS [-5.00(-7, 1)] and VVS [1(-4, 6)] (P < 0.01). When the score was ≤ -2.5, the sensitivity and specificity of the differential diagnosis between CS and VVS were 95.4% and 67.7%, respectively. Since the modified Calgary Syncope Syndrome Score was integer number, CS should be considered when the score was less than -3.</p><p><b>CONCLUSION</b>The modified Calgary Syncope Syndrome Score might be used as an initial diagnostic method in differential diagnosis between CS and VVS, based on the history of the patients.</p>

Sulfur dioxide acts as a novel endogenous gaseous signaling molecule in the cardiovascular system / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Sulfur dioxide was considered to be toxic and detrimental to human health. However, this review highlights recent advances that suggest sulfur dioxide might be a novel endogenous gaseous signaling molecule involved in the regulation of cardiovascular functions.</p><p><b>DATA SOURCES</b>The data used in this review were mainly from the studies reported in Medline and PubMed published from 1986 to 2010.</p><p><b>STUDY SELECTION</b>Original articles and critical reviews selected were relevant to exogenous and endogenous sulfur dioxide.</p><p><b>RESULTS</b>The sulfur dioxide/aspartate amino transferase pathway is endogenously generated in the cardiovascular system, and sulfur dioxide shows broad bioactive effects, such as antihypertension, vasodilation, and amelioration of vascular remodeling. A disturbed sulfur dioxide/aspartate amino transferase pathway is known to be involved in the pathogenesis of many cardiovascular diseases, such as ischemia-reperfusion injury, monocrotaline-induced pulmonary hypertension, athrosclerosis, spontaneous hypertension and hypoxic pulmonary hypertension. Furthermore, in experimental studies the prognosis of these cardiovascular diseases can be improved by targeting endogenous sulfur dioxide.</p><p><b>CONCLUSION</b>The findings suggest that sulfur dioxide is a novel endogenous gaseous signaling molecule involved in the regulation of cardiovascular functions.</p>

A diagnosis-based health economic analysis of postural orthostatic tachycardia syndrome in Chinese children / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Postural orthostatic tachycardia syndrome (POTS) is a common clinical problem in children and adolescents. The previous diagnostic approach to POTS of children and adolescents is based on a series of tests to exclude all other causes, which is time and medical resource consuming. Recently, a new diagnostic approach has been developed. The present study was designed to statistically analyze the results of clinical investigation items and the cost for the diagnosis of POTS in children patients, and evaluate cost changes in the diagnosis of POTS.</p><p><b>METHODS</b>A total of 315 children patients were divided into two groups according to diagnosis period, including group I diagnosed in 2002 - 2006 (100 cases) and group II in 2007 - 2010 (215 cases) and the diagnostic item-based distribution of the cost was analyzed. The diagnostic costs were compared between two groups using SPSS17.0.</p><p><b>RESULTS</b>The per-capita cost of diagnosis in group I was (621.95 ± 21.10) Yuan, costs of diagnostic tests (head-up tilt test, standing test, etc) accounted for 8.68% and the exclusive tests for 91.32%. The per-capita cost of diagnosis in group II was (542.69 ± 23.14) Yuan, diagnostic tests accounted for 10.50% and exclusive tests for 89.50%. Comparison of the total cost of diagnostic tests between the two groups showed significant differences (P < 0.05).</p><p><b>CONCLUSION</b>The cost of POTS diagnosis has been declined in recent years, but the cost of exclusive diagnosis is still its major part.</p>

Predictive role of cerebrospinal fluid hydrogen sulfide in central nervous system leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Central nervous system leukemia (CNSL) is an important relapse in children with acute lymphoblastic leukemia (ALL). We investigated the possible role of endogenous hydrogen sulfide (H(2)S) of cerebrospinal fluid (CSF) in predicting CNSL.</p><p><b>METHODS</b>From August 2008 to December 2010, 380 children were enrolled in this study at Shijitan Hospital, China. These children were from 2 to 16 years old, and the median age was 6.5 years. They were divided into a CNSL group (7 cases), a leukemia group (307 cases), a non-leukemia group (26 cases) and a healthy group (40 children). CSF specimens were obtained from conventional lumbar punctured, then centrifuged and supernatants preserved for H(2)S detection. Leukemic cells precipitates from CSF were found in three cases, the hCSE and hCBS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR), and H(2)S levels in serum were also measured. The receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the predictive diagnosis role of CSF H(2)S in children with ALL and CNSL.</p><p><b>RESULTS</b>The serum H(2)S contents of the CNSL and leukemia groups were (96.98 ± 15.77) µmol/L and (93.35 ± 17.16) µmol/L respectively, much higher than those of healthy, (44.29 ± 2.15) µmol/L, and non-leukemia, (46.32 ± 6.54) µmol/L, groups (P < 0.01). Compared with the leukemia group, CSF H(2)S content of the CNSL group was significantly high (P < 0.01). Meanwhile, in contrast to the non-leukemia group, CSF H(2)S contents of the CNSL and leukemia groups were both significantly increased (P < 0.01). In addition, leukemic cells from CSF precipitations could express CBS and CSE mRNA. Furthermore, the ROC analysis showed the UAC was 0.929 (95%CI: 0.857 - 1.000), and the optimum cut-off value of CSF H(2)S was 12.08 µ mol/L, and the sensitivity and specificity were 83.3% and 97.2% respectively.</p><p><b>CONCLUSIONS</b>CSF H(2)S contents were significantly increased in children with CNSL. After treatment, H(2)S contents were decreased subsequently. Therefore, we speculated that H(2)S levels of CSF would predict CNSL in ALL children.</p>