目的:分析体位性心动过速综合征(postural tachycardia syndrome, POTS)儿童及青少年直立试验过程中血流动力学变化及不同心脏指数(cardiac index, CI)患者血流动力学指标的差异。方法:回顾性分析26例POTS患者与12例健康对照者间直立试...目的:分析体位性心动过速综合征(postural tachycardia syndrome, POTS)儿童及青少年直立试验过程中血流动力学变化及不同心脏指数(cardiac index, CI)患者血流动力学指标的差异。方法:回顾性分析26例POTS患者与12例健康对照者间直立试验过程中总外周血管阻力指数(total peripheral vascular resistance index, TPVRI)、心率和血压的变化,并比较两组间各指标变化趋势。根据每位POTS患者直立试验过程中CI变化趋势将患者分为CI降低组(14例)与CI未降低组(12例),分析两组患者在直立试验过程中CI、TPVRI、心率、血压变化,并比较两组间各指标变化趋势。结果: POTS患者在直立试验过程中CI显著下降( F =6.936, P =0.001),心率明显增快( F = 113.926 , P <0.001),收缩压明显降低( F =6.049, P <0.001),而TPVRI ( F =2.031, P =0.138)和舒张压( F =2.018, P =0.113)无明显变化。健康对照组CI在直立后显著升高( F =3.646, P =0.016),同时心率明显增快( F = 43.970, P <0.001),收缩压( F =4.043, P =0.020)和舒张压( F =8.627, P <0.001)均明显升高,TPVRI ( F = 1.688, P =0.190)无明显变化。POTS患者与健康对照组比较,CI ( F =6.221, P= 0.001)、心率( F =6.203, P < 0.001)和收缩压( F =7.946, P <0.001)随时间变化趋势显著不同,而TPVRI和舒张压在两组间的变化趋势差异无统计学意义( P >0.05)。CI降低组与CI未降低组POTS患者在直立试验中CI变化趋势差异有统计学意义( F = 14.723, P <0.001),前者直立后收缩压明显降低( F =8.010, P <0.001),而后者却无明显变化( F =0.612, P = 0.639 ), TPVRI、心率和舒张压在CI降低组与CI未降低组间随时间变化趋势差异无统计学意义( P >0.05)。年龄是POTS患者直立后CI呈下降趋势的独立影响因素( P =0.013, OR =2.233;95% CI :1.183~4.216)。结论: POTS患者在直立试验过程中存在明显的血流动力学变化,不同患者心输出量变化可能不同,年龄是心输出量下降的独立影响因素。展开更多
Background Abnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated pos...Background Abnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated possible effect of endogenous hydrogen sulfide (H2S) on apoptosis of PASMCs during the development of pulmonary hypertension induced by high pulmonary blood flow. Methods Thirty-nine male Sprague-Dawley rats were randomly assigned to 4-week control, 4-week shunt, 4-week shunt+propargylglycine (PPG), 11-week control, 11-week shunt and 11-week shunt+sodium hydrosulfide (NariS) groups. Rats in 4-week shunt, 4-week shunt+PPG, 11-week shunt and 11-week shunt+NariS groups underwent an abdominal aorta-inferior vena cava shunt. Rats in 4-week shunt+PPG group were intraperitoneally injected with PPG, an inhibitor of endogenous H2S production, for 4 weeks. Rats in 11-week shunt+NariS group were intraperitoneally injected with NariS, a H2S donor, for 11 weeks. Lung tissue H2S was evaluated by sulfide-sensitive electrode. Apoptosis of PASMCs were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). Expressions of Fas, bcl-2 and caspase-3 in the PASMCs were analyzed with immunochemical staining. Results Four weeks after the shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P 〈0.01), but expression of bcl-2 increased significantly (P 〈0.01). PPG administration further inhibited the apoptosis of PASMCs, downregulated the expression of Fas and caspase-3 (P 〈0.01), but increased the expression of bcl-2 (P 〈0.01). After 11 weeks of shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P 〈0.01), but expression of bcl-2 increased obviously (P 〈0.01). NariS administration significantly increased the apoptosis of PASMCs, upregulated the expression of Fas and caspase-3, but inhibited the expression of bcl-2. Conclusions H2S induces the apoptosis of PASMCs in the development of high pulmonary blood flow-induced pulmonary hypertension by activating the Fas pathway and inhibiting the bcl-2 pathway.展开更多
Pulmonary hypertension is a pathophysiologic process characterized by progressive elevation of pulmonary vascular resistance and right heart failure, which is a common complication of many diseases. Pulmonary hyperten...Pulmonary hypertension is a pathophysiologic process characterized by progressive elevation of pulmonary vascular resistance and right heart failure, which is a common complication of many diseases. Pulmonary hypertension with no apparent causes (unknown etiology) is termed primary pulmonary hypertension or, more recently, idiopathic pulmonary arterial hypertension (IPAH). Before the availability of disease-specific (targeted) therapy (through the mid-1980s) the median life expectancy from the time of diagnosis in patients with this disease was 2.8 years. Modem treatment has markedly improved physical function and has extended survival, and the 5-year mortality is 50%. Although there is already more than 100 years of research history, the mechanisms of this disease are still not very clear. Recently, with the development of cell biology and molecular genetics, further research into the mechanisms responsible for pulmonary hypertension have been possible, which has helped in its diagnosis and treatment. It is believed that the mechanisms of pulmonary hypertension can not only be described by pathophysiology but involve multiple factors (pathways) like cellular, humoral and molecular genetics, etc.展开更多
Background Skeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide (H2...Background Skeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide (H2S) iS endogenously produced in mammalian tissues and participates in a number of physiological and pathophysiological processes. We aimed to verify whether H2S could be endogenously generated and released by rat skeletal muscle, and determine the biological effects of H2S in rat skeletal muscle. Methods The study was divided into two parts: detection of endogenous H2S generation and release in rat skeletal muscle and determination of antioxidative activity of skeletal muscle-derived H2S. H2S content and production in tissues were ,detected by sensitive sulfur electrode method. The expressions of H2S producing enzymes cystathionine i^-synthase, cystathionine y-lyase and mercaptopyruvate sulfurtransferase were detected by real-time PCR and western blotting and their tissue distributions were observed by immunohistochemical and immunofluorescent analysis. Rat skeletal muscular ischemia-reperfusion (I-R) injury model was created and evaluated by histological analysis under microscope. The malondialdehyde (MDA) contents, hydrogen peroxide levels, superoxide anion and superoxide dismutase (SOD) activities were detected using spectrophotometer. Results H2S could be endogenously generated and released by skeletal muscle of Sprague-Dawley rats (H2S content: (2.06+0.43) nmol/mg; H2S production: (0.17+0.06) nmol.minl.mgl). Gene and protein expressions of the three H2S producing enzymes ~vere detected in skeletal muscle, as well as the liver and kidney. Endogenous H2S content and production were decreased in skeletal muscles of rats with I-R skeletal muscle injury (P 〈0.05). Furthermore, H2S significantly protected rat skeletal muscle against I-R injury and resulted in decreased MDA content, reduced hydrogen peroxide and superoxide anion levels, but increased SOD activity and protein expression in skeletal muscles (all P 〈0.01). Conclusion H2S generation pathway exists in rat skeletal muscle and it acts as an antioxidant in skeletal muscle.展开更多
Background 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 (H2S) of cerebrospi...Background 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 (H2S) of cerebrospinal fluid (CSF) in predicting CNSL. Methods 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 H2S 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 H2S 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 H2S in children with ALL and CNSL. Results The serum H2S contents of the CNSL and leukemia groups were (96.98±15.77) pmol/L and (93.35±17.16) μmol/L respectively, much higher than those of healthy, (44.29±2.15) pmol/L, and non-leukemia, (46.32±6.54) μmol/L, groups (P 〈0.01). Compared with the leukemia group, CSF H2S content of the CNSL group was significantly high (P 〈0.01). Meanwhile, in contrast to the non-leukemia group, CSF H2S 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 H2S was 12.08μmol/L, and the sensitivity and specificity were 83.3% and 97.2% respectively. Conclusions CSF H2S contents were significantly increased in children with CNSL. After treatment, H2S contents were decreased subsequently. Therefore, we speculated that H2S levels of CSF would predict CNSL in ALL children.展开更多
Background Atherosclerosis is an important cardiovascular disease, becoming a major and increasing health problem in developed countries. However, the possible underlying mechanisms were not completely clear. In 2009,...Background Atherosclerosis is an important cardiovascular disease, becoming a major and increasing health problem in developed countries. However, the possible underlying mechanisms were not completely clear. In 2009, our research group first discovered that hydrogen sulfide (H2S) as a novel gastrotransmitter played an important anti-atherosclerotic role. The study was designed to examine the regulatory effect of hydrogen sulfide (H2S) on endoplasmic reticulum stress (ERS) in apolipoprotein E knockout (apoE/) mice fed a Western type diet. Methods C57BL/6 mice and homozygous apoE/ mice were fed a Western type diet. C57BL/6 mice were injected intraperitoneally with normal saline (5 ml/kg per day) as control group. The apoE/ mice were treated with the same dose of normal saline as the apoE/ group, injected intraperitoneally with sodium hydrosulfide (NariS, an H2S donor, 56 IJmol/kg per day) as the apoE/+NaHS group and injected intraperitoneally with DL-propargylglycine (PPG, a cystathionine-y-lyase inhibitor, 50 mg/kg, per day) as the apoE/ +PPG group. After 10 weeks, the mice were sacrificed and the plasma lipids were detected. Sections of aortic root from these animals were examined for atherosclerotic lesions by HE and oil red O staining. The aortic ultrastructure and microstructure were analyzed with the help of light and electronic microscope. Glucose-regulated protein 78 (GRP78), caspase-12, copper-andzinc-containing superoxide dismutase (Cu/ZnSOD) and Mn-containing superoxide dismutase (MnSOD) protein expression in aortic tissues were detected with immunohistochemistry. The level of intracellular reactive oxygen species (ROS) were measured by using a commercial assay kit. Results Compared with control mice, apoE/ mice showed increased plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL), decreased high density lipoprotein (HDL), increased aortic plaque size, destroyed ultra-structure of aortic tissue, and increased expression of GRP78 and caspase-12 proteins. Compared with apoE/ mice, H2S donor-treated apoE-/- mice showed a decreased plasma LDL level, lessened plaque necrosis and attenuated aortic ultra-structural disorder. H2S donor-treatment induced GRP78 expression but suppressed caspase-12 expression in aortic lesions. However, compared with apoE-/- mice, PPG treated apoE/ mice showed enlarged plaque size, more severe ultrastructural disorder of the aortic tissue and reduced GRP78 staining in aortic lesions. The plasma lipids and the staining of caspase-12 in apoE-/+ PPG rats did not significantly differ from those in the apoE-/- mice. Consistently, H2S induced SOD expression, accompanied by a reduced level of ROS. Conclusion H2S plays a regulatory role in aortic ERS and reduces atherosclerotic lesions in apoE-/-mice fed with a Western type diet.展开更多
Objective 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 i...Objective 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. Data sources The data used in this review were mainly from the studies reported in Medline and PubMed published from 1986 to 2010. Study selection Original articles and critical reviews selected were relevant to exogenous and endogenous sulfur dioxide. Results 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. Conclusion The findings suggest that sulfur dioxide is a novel endogenous gaseous signaling molecule involved in the regulation of cardiovascular functions.展开更多
Background 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 test...Background 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. Methods 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. Results The per-capita cost of diagnosis in group I was (621.95±2.1.10) 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±2.3.14) 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). Conclusion The cost of POTS diagnosis has been declined in recent years, but the cost of exclusive diagnosis is still its major part.展开更多
Background Syncope is a common clinical problem with multiple causes. Vasovagal syncope (VVS) is by far the most frequent cause of syncope in children and adolescents. The traditional diagnostic approach to VVS of c...Background Syncope is a common clinical problem with multiple causes. Vasovagal syncope (VVS) is by far the most frequent cause of syncope in children and adolescents. The traditional diagnostic approach to VVS of children and adolescents is based on a series of tests to exclude all other causes, which is complex and time and medical resource consuming. Attempts have been made to develop a new cost-effective diagnostic approach to avoid these problems. This study aimed to compare the economic effectiveness and diagnostic value of the traditional diagnostic approach to VVS of children with a new diagnostic approach. Methods One hundred and eighteen children diagnosed as VVS were divided into two groups according to the different diagnostic approaches. The diagnostic value of the two diagnostic approaches was then analyzed. Meanwhile, the costs of hospitalization, diagnostic testing and hospital stay were determined. Data were evaluated by the cost-minimization analysis. Results The diagnostic value of the new diagnostic approach was similar to that of the traditional diagnostic approach (56.57% vs. 53.91%, P=0.697). However, the cost of hospitalization per patient by the new diagnostic approach was (1507.08±144.63) Yuan (RMB) which was less than that of the traditional diagnostic approach (2603.64±2.08.19) Yuan. The costs of diagnostic tests per patient by the new diagnostic approach was (1256.04±109.14) Yuan and by the traditional approach (2175.22±153.32) Yuan. Conclusion Compared to the traditional diagnostic approach to diagnose VVS in children and adolescents, the new diagnostic approach is of a good economic value, and it should be popularized in clinical practice.展开更多
Previously,hydrogen sulfide (H2S) was considered to be a toxic gas. However, recently it was discovered that it could be produced in mammals and even in plants, through the production and metabolism of sulfur-contai...Previously,hydrogen sulfide (H2S) was considered to be a toxic gas. However, recently it was discovered that it could be produced in mammals and even in plants, through the production and metabolism of sulfur-containing amino acids.展开更多
文摘目的:分析体位性心动过速综合征(postural tachycardia syndrome, POTS)儿童及青少年直立试验过程中血流动力学变化及不同心脏指数(cardiac index, CI)患者血流动力学指标的差异。方法:回顾性分析26例POTS患者与12例健康对照者间直立试验过程中总外周血管阻力指数(total peripheral vascular resistance index, TPVRI)、心率和血压的变化,并比较两组间各指标变化趋势。根据每位POTS患者直立试验过程中CI变化趋势将患者分为CI降低组(14例)与CI未降低组(12例),分析两组患者在直立试验过程中CI、TPVRI、心率、血压变化,并比较两组间各指标变化趋势。结果: POTS患者在直立试验过程中CI显著下降( F =6.936, P =0.001),心率明显增快( F = 113.926 , P <0.001),收缩压明显降低( F =6.049, P <0.001),而TPVRI ( F =2.031, P =0.138)和舒张压( F =2.018, P =0.113)无明显变化。健康对照组CI在直立后显著升高( F =3.646, P =0.016),同时心率明显增快( F = 43.970, P <0.001),收缩压( F =4.043, P =0.020)和舒张压( F =8.627, P <0.001)均明显升高,TPVRI ( F = 1.688, P =0.190)无明显变化。POTS患者与健康对照组比较,CI ( F =6.221, P= 0.001)、心率( F =6.203, P < 0.001)和收缩压( F =7.946, P <0.001)随时间变化趋势显著不同,而TPVRI和舒张压在两组间的变化趋势差异无统计学意义( P >0.05)。CI降低组与CI未降低组POTS患者在直立试验中CI变化趋势差异有统计学意义( F = 14.723, P <0.001),前者直立后收缩压明显降低( F =8.010, P <0.001),而后者却无明显变化( F =0.612, P = 0.639 ), TPVRI、心率和舒张压在CI降低组与CI未降低组间随时间变化趋势差异无统计学意义( P >0.05)。年龄是POTS患者直立后CI呈下降趋势的独立影响因素( P =0.013, OR =2.233;95% CI :1.183~4.216)。结论: POTS患者在直立试验过程中存在明显的血流动力学变化,不同患者心输出量变化可能不同,年龄是心输出量下降的独立影响因素。
基金This work was supported by grants from the Foundation of the Ministry of Education, China (No. 20070001702, 20070001770), the National Natural Science Foundation of China (No. 30630031, 30821001, 30801251), the Major Basic Research Development Program of China (No. 2006CB503807) and Beijing Natural Science Foundation (No. 7072082).
文摘Background Abnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated possible effect of endogenous hydrogen sulfide (H2S) on apoptosis of PASMCs during the development of pulmonary hypertension induced by high pulmonary blood flow. Methods Thirty-nine male Sprague-Dawley rats were randomly assigned to 4-week control, 4-week shunt, 4-week shunt+propargylglycine (PPG), 11-week control, 11-week shunt and 11-week shunt+sodium hydrosulfide (NariS) groups. Rats in 4-week shunt, 4-week shunt+PPG, 11-week shunt and 11-week shunt+NariS groups underwent an abdominal aorta-inferior vena cava shunt. Rats in 4-week shunt+PPG group were intraperitoneally injected with PPG, an inhibitor of endogenous H2S production, for 4 weeks. Rats in 11-week shunt+NariS group were intraperitoneally injected with NariS, a H2S donor, for 11 weeks. Lung tissue H2S was evaluated by sulfide-sensitive electrode. Apoptosis of PASMCs were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). Expressions of Fas, bcl-2 and caspase-3 in the PASMCs were analyzed with immunochemical staining. Results Four weeks after the shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P 〈0.01), but expression of bcl-2 increased significantly (P 〈0.01). PPG administration further inhibited the apoptosis of PASMCs, downregulated the expression of Fas and caspase-3 (P 〈0.01), but increased the expression of bcl-2 (P 〈0.01). After 11 weeks of shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P 〈0.01), but expression of bcl-2 increased obviously (P 〈0.01). NariS administration significantly increased the apoptosis of PASMCs, upregulated the expression of Fas and caspase-3, but inhibited the expression of bcl-2. Conclusions H2S induces the apoptosis of PASMCs in the development of high pulmonary blood flow-induced pulmonary hypertension by activating the Fas pathway and inhibiting the bcl-2 pathway.
基金This work was supported by the grants from Changjiang Scholars Program (No. 985-2-087-111), the National Science Foundation for Distinguished Young Scholars (No. 30425010), the Major State Basic Research Development Program of China (No. 2006CB503807), the Research Fund for the Doctoral Program of Ministry of Education of China (No. 20070001702 and No. 20070001770) and the National Natural Science Foundation of China (No. 30630031).
文摘Pulmonary hypertension is a pathophysiologic process characterized by progressive elevation of pulmonary vascular resistance and right heart failure, which is a common complication of many diseases. Pulmonary hypertension with no apparent causes (unknown etiology) is termed primary pulmonary hypertension or, more recently, idiopathic pulmonary arterial hypertension (IPAH). Before the availability of disease-specific (targeted) therapy (through the mid-1980s) the median life expectancy from the time of diagnosis in patients with this disease was 2.8 years. Modem treatment has markedly improved physical function and has extended survival, and the 5-year mortality is 50%. Although there is already more than 100 years of research history, the mechanisms of this disease are still not very clear. Recently, with the development of cell biology and molecular genetics, further research into the mechanisms responsible for pulmonary hypertension have been possible, which has helped in its diagnosis and treatment. It is believed that the mechanisms of pulmonary hypertension can not only be described by pathophysiology but involve multiple factors (pathways) like cellular, humoral and molecular genetics, etc.
基金The study was supported by the grants from Major Basic Research Development Program of People's Republic of China (No. 2011CB503904 and No. 2013CB933801) and National Natural Science Foundation of China (No. 81070212).
文摘Background Skeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide (H2S) iS endogenously produced in mammalian tissues and participates in a number of physiological and pathophysiological processes. We aimed to verify whether H2S could be endogenously generated and released by rat skeletal muscle, and determine the biological effects of H2S in rat skeletal muscle. Methods The study was divided into two parts: detection of endogenous H2S generation and release in rat skeletal muscle and determination of antioxidative activity of skeletal muscle-derived H2S. H2S content and production in tissues were ,detected by sensitive sulfur electrode method. The expressions of H2S producing enzymes cystathionine i^-synthase, cystathionine y-lyase and mercaptopyruvate sulfurtransferase were detected by real-time PCR and western blotting and their tissue distributions were observed by immunohistochemical and immunofluorescent analysis. Rat skeletal muscular ischemia-reperfusion (I-R) injury model was created and evaluated by histological analysis under microscope. The malondialdehyde (MDA) contents, hydrogen peroxide levels, superoxide anion and superoxide dismutase (SOD) activities were detected using spectrophotometer. Results H2S could be endogenously generated and released by skeletal muscle of Sprague-Dawley rats (H2S content: (2.06+0.43) nmol/mg; H2S production: (0.17+0.06) nmol.minl.mgl). Gene and protein expressions of the three H2S producing enzymes ~vere detected in skeletal muscle, as well as the liver and kidney. Endogenous H2S content and production were decreased in skeletal muscles of rats with I-R skeletal muscle injury (P 〈0.05). Furthermore, H2S significantly protected rat skeletal muscle against I-R injury and resulted in decreased MDA content, reduced hydrogen peroxide and superoxide anion levels, but increased SOD activity and protein expression in skeletal muscles (all P 〈0.01). Conclusion H2S generation pathway exists in rat skeletal muscle and it acts as an antioxidant in skeletal muscle.
基金This work was supported by grants from National Natural Science Foundation of China (No. 30821001, No. 30801251 and No. 81070212) and Beijing Natural Science Foundation (No. 7093136).
文摘Background 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 (H2S) of cerebrospinal fluid (CSF) in predicting CNSL. Methods 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 H2S 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 H2S 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 H2S in children with ALL and CNSL. Results The serum H2S contents of the CNSL and leukemia groups were (96.98±15.77) pmol/L and (93.35±17.16) μmol/L respectively, much higher than those of healthy, (44.29±2.15) pmol/L, and non-leukemia, (46.32±6.54) μmol/L, groups (P 〈0.01). Compared with the leukemia group, CSF H2S content of the CNSL group was significantly high (P 〈0.01). Meanwhile, in contrast to the non-leukemia group, CSF H2S 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 H2S was 12.08μmol/L, and the sensitivity and specificity were 83.3% and 97.2% respectively. Conclusions CSF H2S contents were significantly increased in children with CNSL. After treatment, H2S contents were decreased subsequently. Therefore, we speculated that H2S levels of CSF would predict CNSL in ALL children.
基金This work was supported by the grants from the Major Basic Research Development Program of China (No. 2011CB503904, No. 2012CB517806) and from the National Natural Science Foundation of China (No. 81070212, No. 30821001 and No. 30801251).
文摘Background Atherosclerosis is an important cardiovascular disease, becoming a major and increasing health problem in developed countries. However, the possible underlying mechanisms were not completely clear. In 2009, our research group first discovered that hydrogen sulfide (H2S) as a novel gastrotransmitter played an important anti-atherosclerotic role. The study was designed to examine the regulatory effect of hydrogen sulfide (H2S) on endoplasmic reticulum stress (ERS) in apolipoprotein E knockout (apoE/) mice fed a Western type diet. Methods C57BL/6 mice and homozygous apoE/ mice were fed a Western type diet. C57BL/6 mice were injected intraperitoneally with normal saline (5 ml/kg per day) as control group. The apoE/ mice were treated with the same dose of normal saline as the apoE/ group, injected intraperitoneally with sodium hydrosulfide (NariS, an H2S donor, 56 IJmol/kg per day) as the apoE/+NaHS group and injected intraperitoneally with DL-propargylglycine (PPG, a cystathionine-y-lyase inhibitor, 50 mg/kg, per day) as the apoE/ +PPG group. After 10 weeks, the mice were sacrificed and the plasma lipids were detected. Sections of aortic root from these animals were examined for atherosclerotic lesions by HE and oil red O staining. The aortic ultrastructure and microstructure were analyzed with the help of light and electronic microscope. Glucose-regulated protein 78 (GRP78), caspase-12, copper-andzinc-containing superoxide dismutase (Cu/ZnSOD) and Mn-containing superoxide dismutase (MnSOD) protein expression in aortic tissues were detected with immunohistochemistry. The level of intracellular reactive oxygen species (ROS) were measured by using a commercial assay kit. Results Compared with control mice, apoE/ mice showed increased plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL), decreased high density lipoprotein (HDL), increased aortic plaque size, destroyed ultra-structure of aortic tissue, and increased expression of GRP78 and caspase-12 proteins. Compared with apoE/ mice, H2S donor-treated apoE-/- mice showed a decreased plasma LDL level, lessened plaque necrosis and attenuated aortic ultra-structural disorder. H2S donor-treatment induced GRP78 expression but suppressed caspase-12 expression in aortic lesions. However, compared with apoE-/- mice, PPG treated apoE/ mice showed enlarged plaque size, more severe ultrastructural disorder of the aortic tissue and reduced GRP78 staining in aortic lesions. The plasma lipids and the staining of caspase-12 in apoE-/+ PPG rats did not significantly differ from those in the apoE-/- mice. Consistently, H2S induced SOD expression, accompanied by a reduced level of ROS. Conclusion H2S plays a regulatory role in aortic ERS and reduces atherosclerotic lesions in apoE-/-mice fed with a Western type diet.
基金This work was supported by the grants from the National Natural Science Foundation of China (No. 81070111, No. 30821001 and No. 30801251), the Major State Basic Research Development Program (No. 2011CB503904) and the Natural Science Foundation of Beijing (No. 7112130).
文摘Objective 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. Data sources The data used in this review were mainly from the studies reported in Medline and PubMed published from 1986 to 2010. Study selection Original articles and critical reviews selected were relevant to exogenous and endogenous sulfur dioxide. Results 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. Conclusion The findings suggest that sulfur dioxide is a novel endogenous gaseous signaling molecule involved in the regulation of cardiovascular functions.
文摘Background 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. Methods 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. Results The per-capita cost of diagnosis in group I was (621.95±2.1.10) 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±2.3.14) 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). Conclusion The cost of POTS diagnosis has been declined in recent years, but the cost of exclusive diagnosis is still its major part.
文摘Background Syncope is a common clinical problem with multiple causes. Vasovagal syncope (VVS) is by far the most frequent cause of syncope in children and adolescents. The traditional diagnostic approach to VVS of children and adolescents is based on a series of tests to exclude all other causes, which is complex and time and medical resource consuming. Attempts have been made to develop a new cost-effective diagnostic approach to avoid these problems. This study aimed to compare the economic effectiveness and diagnostic value of the traditional diagnostic approach to VVS of children with a new diagnostic approach. Methods One hundred and eighteen children diagnosed as VVS were divided into two groups according to the different diagnostic approaches. The diagnostic value of the two diagnostic approaches was then analyzed. Meanwhile, the costs of hospitalization, diagnostic testing and hospital stay were determined. Data were evaluated by the cost-minimization analysis. Results The diagnostic value of the new diagnostic approach was similar to that of the traditional diagnostic approach (56.57% vs. 53.91%, P=0.697). However, the cost of hospitalization per patient by the new diagnostic approach was (1507.08±144.63) Yuan (RMB) which was less than that of the traditional diagnostic approach (2603.64±2.08.19) Yuan. The costs of diagnostic tests per patient by the new diagnostic approach was (1256.04±109.14) Yuan and by the traditional approach (2175.22±153.32) Yuan. Conclusion Compared to the traditional diagnostic approach to diagnose VVS in children and adolescents, the new diagnostic approach is of a good economic value, and it should be popularized in clinical practice.
文摘Previously,hydrogen sulfide (H2S) was considered to be a toxic gas. However, recently it was discovered that it could be produced in mammals and even in plants, through the production and metabolism of sulfur-containing amino acids.