During ischemia, the intracellular acidosis stimulates the Na +/H + exchanger. The increase in intracellular sodium secondary to increased Na +/H + exchange is reversed through exchange for calcium, resulting in calcium overload of the cells and producing cell injury and necrosis. NHE1 inhibitors exert a protective effect on myocardium subject to ischemia and reperfusion via reduction of Na +/H + exchange, attenuation of intracellular calcium accumulation and other mechanisms.

Na +/H + exchanger 1 (NHE1) is a major contributor to ischemic and reperfusion injury. It is emerging that NHE 1 also contributes to myocardial hypertrophy and heart failure due to chronic maladaptive stimulation. It appears that NHE 1 may represent a common downstream mediator for various hypertrophic factor, such as angiotensinⅡ,beta (1) and alpha (1) adrenergic receptor activation. NHE 1 inhibition may be a effective new therapeutic approach for prevention and treatment of heart failure.-

Objective To observe the effects of low-dose theophylline and tiotropium on lung function and quality of life in patients with mild-moderate stable chronic obstructive pulmonary disease (COPD) and evaluate its safety.Methods This was a randomized,parallel-group,controlled trial.A total of 115 patients with mild-moderate stable COPD were divided into tiotropium group (37 cases),slow-release theophylline group (40 cases) and the combination of slow-release theophylline and tiotropium group (38 cases) by random digits table method.Thirty-eight patients without cardiopulmonary diseases were enrolled in control group.Observation period was 12 months.The lung function,6 min walking test distance (6MWD),modified British Medical Research Council Scale (mMRC),and COPD assessment test (CAT) were monitored before treatment and after treatment for 12 months.Results Of 115 patients,107 patients (35cases in tiotropium group,36 cases in slow-release theophylline group and 36 cases in combination of slowrelease theophylline and tiotropium group) completed the study.No significant difference was found in spirometry parameters reflecting airflow limitation after 12 months treatment compared with that before treatment in tiotropium group,slow-release theophylline group and the combination of slow-release theophylline and tiotropium group (P ＞ 0.05),such as the percentage of forced expiratory volume in 1 second (FEV1) over the expected value (FEV1％) and FEV1/forced vital capacity (FVC).The percentage of mid expiratory flow over the expected value (FEF25～75％) was improved in all groups,but the increment of FEF25～75 ％ was much higher in tiotropium group and the combination of slow-release theophylline and tiotropium group than that in slow-release theophylline group:(39.23 ± 7.77)％,(39.99 ± 8.25)％ vs.(34.91 ± 9.50)％,there were significant differences (P ＜ 0.05).Similar changes were observed in mMRC and CAT score.There was significant difference in CAT score between tiotropium group,the combination of slow-release theophylline and tiotropium group and slow-release theophylline group:(14.34 ± 2.22),(14.39 ± 3.53) scores vs.(16.22 ± 3.35) scores,P ＜ 0.05.6MWD was no obvious change in tiotropium group,slow-release theophylline group and the combination of slow-release theophylline and tiotropium group before and after treatment.The use frequency of short-acting drugs bronchiectasis was the lowest in the combination of slow-release theophylline and tiotropium group,and only was (2.3 ± 1.4) times per week.Fourteen patients happened COPD exacerbations in slow-release theophylline group during 12 months treatment.The duration in slow-release theophylline group was more than that in tiotropium group and the combination of slow-release theophylline and tiotropium group:(9.76 ± 2.25) d vs.(7.85 ± 2.51),(8.29 ± 2.24) d,and there was significant difference (P ＜ 0.05).Conclusions For mild-moderate stable COPD patients,the quality of life and dyspnea scores are not improved significantly after treatment of low-dose slow-release theophylline,and the combination slow-release theophylline and tiotropium may be more beneficial and safe.

Objective: To prepare a blood deficient model and study the effect of Tangkuei Blood Supplementing Decoction on hemopoiesis in this model. Methods: This model was made in mice by i.p. an accumulate doses of 60mg/kg acetylphenylhydrazine (APH) and 160mg/kg cyclophosphamidum (CY). The RBCs, WBCs, reticulocytes and bone marrow nucleated cells (BMNC) were counted, the micro structure of bone marrow was observed. The swimming time, the body temperature and the plasma cAMP, cGMP levels were measured. The effects of Tangkuei Blood Supplementing Decoction by p.o. administration on promoting the hemopioetic function were observed with the model mice. Results: Tangkuei Blood Supplementing Decoction could remarkably increase RBC, WBC, BMNC, improve the proportion of reticulolytes in peripheral blood and the micro struture of bone marrow, prolony the swimming time, raise the body temperature and the specific value of cAMP/cGMP. Conclusion: The model exhibits the main features of blood deficiency, and can be used as one of models of blood deficiency. Tangkuei Blood Supplementing Decoction can obviously improve the dual deficiention of qi and blood of model mice by supplementing qi and blood.

Object To study the liver-protection and bile promoting secretion of gentiopicroside administrated ig in rat. Methods Gentiopicroside was administrated ig to the mice with liver injury induced by CCl 4 and D-GlaN. ALT, AST levels in serum and GSH-Px activity in liver were examined. The bile flow rate and the concentration of the main components in the bile of rats after ig administration of gentiopicroside were estimated. Results Gentiopicroside administrated ig decreased the serum ALT and AST levels, increased the liver GSH-Px activity in the mice treated with CCl 4, promoted the secretion of bile and increased the concentration of bilirubin in the bile. Conclusion Gentiopicroside administrated ig exhibited significant liver-protection and promoting bile secretion.

OBJECTIVETo observe the effect of single administration of mercury- containing preparation Jiuyi Dan (calcined gypsum-Shengdan 9: 1) and Shengdan on acute toxicity of rabbits, in order to assess the safety of tested drugs.

METHODThe rabbits were randomly divided into 4 groups: the calcined gypsum group (excipient control), the Jiuyi Dan group, the 90 mg Shengdan group and the 180 mg Shengdan group. After 270 mg of calcined gypsum, 300 mg of Jiuyi Dan, 90 mg of Shengdan, and 180 mg of Shengdan were used on the surface of wounds (5 cm x 5 cm) on two sides of rabbit back for 5 h, the surfaces of wound were washed by water. The bloods were taken from the rabbit hearts before and after the drug administration for 24 h, 72 h, 7 d and 14 d for determining Hg level in blood and liver & kidney function indicators (ALT, AST, CREAT, and BUN). The rabbits were dissected after the drugs treatment for 14 d, and pathological tests were made for their livers and kidneys.

RESULTCompared with the calcined gypsum group, the 90 mg Shengdan group and the 180 mg Shengdan group showed significant increase (P < 0.01 or P < 0.05), as evidenced by increase in CREAT for 24 h and 72 h and increase in BUN for 24 h and on 7 d. AST is significantly increased as well (P < 0.01) for 24 h and 72 h compared to that of the group before drug treatment. The Hg level in blood was significantly enhanced (P < 0.01) after the rabbits were administrated with drugs for 24 h to 72 h. The pathological changes in livers and kidneys of rabbits were observed in the two doses of Shengdan treatment groups.

CONCLUSIONThe Hg blood levels were increased significantly in an obvious dose-effect relationship in all drugs treatment groups. Liver & kidney function indicators were influenced by Shengdan treatment to some extent. Meanwhile, pathological changes in rabbit livers and kidneys were also caused by Shengdan, while Jiuyi Dan has no significantly effect on livers and kidneys.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Creatinine ; blood ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Kidney ; drug effects ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; urine ; Rabbits ; Random Allocation ; Skin ; drug effects ; injuries ; Time Factors ; Toxicity Tests, Acute

OBJECTIVETo observe the changes of the blood and urine mercury (Hg) levels and liver & kidney functions of rabbits after administration of Jiuyi Dan (calcined gypsum-Sheng Dan 9: 1) for 1 month and the recovery of rabbits after the drug withdrawal.

METHODThe rabbits were randomly divided into 2 groups: the calcined gypsum group and the Jiuyi Dan group. After 36 mg of calcined gypsum and 40 mg of Jiuyi Dan were used on the surface of wound (5 cm x 5 cm) on one side of rabbit back for 4 h, the surfaces of wound were washed by saline. The bloods were taken from the rabbit hearts before and after the drug administration for 14 and 28 days, and after the drug withdrawal for 7, 40, 71, and 92 days for determining Hg level in blood, and liver & kidney function indicators (ALT, AST, CREAT and BUN). The Hg level in urine collected from bladders was examined while rabbits were dissected after the drug withdrawal for 1, 40, 71, and 92 days.

RESULTThe Hg level in blood was significantly increased (P < 0.01) after the rabbits were administrated with drugs for 14 and 28 days and after the drug treatment was stopped for 7 and 40 days. The Hg level in urine was significantly enhanced after the drug withdrawal for 1, 40, 71 days. However, the liver & kidney indicators were not influenced.

CONCLUSIONThe Hg level in rabbit blood and urine was significantly increased after the consecutive administration of double-dose Jiuyi Dan for 1 month. However, the blood Hg level and urine Hg level recover after the drug withdrawal for 71 days and 3 months, respectively. The liver & kidney indicators do not significantly change with the dose.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Kidney ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mercury ; blood ; metabolism ; urine ; Rabbits ; Random Allocation ; Skin ; drug effects ; injuries ; Time Factors

Objective To compare the hepatotoxicity of matrine (MT) and oxymatrine (OMT) and explore the severity and characteristics of their toxicity, and to preliminarily elucidate their toxic mechanisms. Methods Liver cell line LO-2 cells were treated with acetaminophen (APAP), matrine and oxymatrine for 24 h, and the IC values, the contents of enzymes in the liver cells, the pathological changes, the contents of malondialdehyde (MDA) and glutathione (GSH) and the cell apoptosis rate were detected. In addition, adult zebrafish were treated with APAP, matrine and oxymatrine for 96 h, and the LC50 values, the pathological morphology of the liver cells, the contents of MDA and GSH and the apoptosis rate were detected. Meanwhile, the expression of oxidative stress-related gene, zgc: 136383, and the apoptosis-related genes, EIF4EBP3 and zgc: 123120, was also detected. Results Matrine and oxymatrine had toxic effects on liver cells in vitro. The IC50 value of matrine was 5. 3 mmol/L, and that of oxymatrine was ＞ 19 mmol/L. The contents of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the liver cells treated with matrine or oxymatrine were increased, and the cells appeared swollen, with an increase in the MDA level and a decrease in the GSH level. The cell apoptosis rate was also increased (P ＜ 0. 05). Furthermore, matrine and oxymatrine had toxic effects on the zebrafish. The LC50 value of matrine was 0. 41 mmol/L, and that of oxymatrine was ＞3. 8 mmol/L. The hepatocytes of zebrafish treated with matrine and oxymatrine appeared vacuolization in a mild to moderate degree, with an increase of the MDA content and a decrease of the GSH content. The cell apoptosis rate was increased (P ＜0. 05 for all). Expression of the oxidative stress-related gene zgc: 136383 (P ＜ 0. 05) and the apoptosis-resistant gene EIF4EBP3 (P ＜ 0. 05) was down-regulated by matrine, but that of the apoptosis-promoting gene zgc: 123120 was up-regulated (P ＜ 0. 05). Conclusions Results of the experiments using liver cells in vitro are consistent with those using the in vivo zebrafish model. Matrine (MT) and oxymatrine (OMT) both have hepatotoxicity, with similar toxic characteristics, and the toxicity of matrine is greater than oxymatrine. The mechanism of their hepatotoxicity is related with oxidative stress and cell apoptosis. Matrine reduces lipid transportation and activates oxidative stress reactions through down-regulation of gene zgc: 136383. In addition, matrine induces apoptosis in the liver cells via up-regulation of the apoptosis-promoting gene zgc: 123120 and down-regulation of the apoptosis-resistant gene EIF4EBP3.

Objective To investigate the clinical value of abnormal course of fetal superior mesenteric arteries (SMA) detected by ultrasound during the first trimester (11-13+6 weeks) in predicting congenital diaphragmatic hernia (CDH). Methods This study enrolled women who underwent fetal nuchal translucency (NT) screening during the first trimester in Central Hospital of Panyu District from March to December 2017. Low-speed high-definition flow imaging was used to observe the course of fetal SMA, and it was regarded as abnormal when the angle between SMA and abdominal aorta >90°. Once abnormal course of the SMA was suspected, the position of fetal thoracic cavity and abdominal organs would be scanned carefully. Furthermore, ultrasound examinations would be repeated at 16-18, 20-24, 28-32 and 37-40 weeks of gestation. Fetus diagnosed as CDH by ultrasound would be scheduled for MRI or autopsy to confirm the diagnosis. Pregnancy outcomes of all cases were followed up by telephone. Descriptive statistical analysis was used in this study. Results A total of 6 899 gravidas (6 964 fetuses) underwent NT scan during the first trimester were enrolled and the SMA of all fetuses were successfully displayed. Three cases with abnormal course of the SMA were identified. Two of them were diagnosed with left CDH at 17+ and 23+ weeks of gestation, which was confirmed by autopsy after termination of pregnancy, and the other one terminated pregnancy in first trimester due to a large omphalocele. Among the 6 961 fetuses with normal SMA, the pregnancy outcomes of 6 120 were successfully followed up, only one of which was found to have left CDH at 32 gestational weeks by ultrasound examination, and was later confirmed by neonatal MRI after delivery. No other fetal CDH was detected. Conclusions Abnormal course of the SMA identified in early pregnancy may be a simple and effective indicator for CDH that allow early intervention and treatment.