Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study / 中国当代儿科杂志

OBJECTIVES@#To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.@*METHODS@#A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.@*RESULTS@#Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).@*CONCLUSIONS@#This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

Protective Effect of Modified Sinisan on Depression-induced Liver Injury in Rat / 中国实验方剂学杂志

Objective:To study the protective effect of modified Sinisan on liver injury caused by chronic unpredictable mild stress (CUMS) combined with solitary nutrition method based on a depression model. Method:Forty-eight SD male rats were randomly divided into normal group, depression model group, fluoxetine group (1.58 mg·kg-1·d-1), and low, medium and high-dose modified Sinisan (3.67, 7.34, 14.68 g·kg-1·d-1) groups, with 8 rats in each group. After the administration of the model, the levels of alanine aminotransferase（ALT）, aspartate aminotransferase（AST） in serum and the levels of inflammatory factors tumor necrosis factor-α（TNF-α）, interleukin（IL）-1β, and IL-6 in liver tissues were measured by a biochemical kit method. Western blot was used to detect the expressions of cysteine aspastic acid-specific protease-3 (Caspase-3) and cleaved Caspase-3 in liver cells after intervention with modified Sinisan. Result:Compared with the normal group, the biochemical test showed that the levels of ALT and AST in the serum of the model group were significantly increased (P<0.05), and the levels of inflammatory factors TNF-α, IL-1β and IL-6 in liver tissue significantly increased (P<0.05). Compared with the model group, low, medium-dose modified Sinisan groups significantly reduced serum ALT, AST and inflammatory factors TNF-α, IL-1β and IL-6 levels (P<0.05). Western blot showed that compared with the normal group, the protein expression of Caspase-3 in model rat liver cells decreased, while the protein expression of cleaved Caspase-3 increased（P<0.05，P<0.01）. Compared with the model group, low, medium-dose modified Sinisan groups could up-regulate Caspase-3 protein expression, and down-regulated the expression of cleaved Caspase-3 protein（P<0.05，P<0.01）. Conclusion:Chronic stress-induced depression model can cause liver damage. Modified Sinisan can have the hepatoprotective effect by regulating the levels of various physiological, biochemical and inflammatory factor indicators, and inhibiting liver cell apoptosis.

Safety and efficacy of caffeine use started at different time in preterm infants: a multicenter study in Jiangsu Province, China / 中国当代儿科杂志

OBJECTIVE@#To study the efficacy and safety of caffeine used in the early (≤72 hours after birth) and late (>72 hours after birth) stage in preterm infants with a gestational age of ≤31 weeks.@*METHODS@#A retrospective analysis was performed for 640 preterm infants (with a gestational age of ≤31 weeks) who were admitted to the neonatal intensive care unit of eight hospitals in Jiangsu Province, China. Of the 640 preterm infants, 510 were given caffeine in the early stage (≤72 hours after birth; early use group) and 130 were given caffeine in the late stage (>72 hours after birth; late use group). The clinical data were compared between the two groups.@*RESULTS@#There were no significant differences in birth weight, Apgar score, sex, gestational age, and age on admission between the two groups (P>0.05). Compared with the late use group, the early use group had a significantly younger age at the beginning and withdrawal of caffeine treatment (P0.05). Compared with the late use group, the early use group had significantly lower incidence rate of apnea (P0.05). However, significant differences were found in the incidence of bronchopulmonary dysplasia and the rate of home oxygen therapy, but there was no significant difference in the mortality rate between the two groups (P>0.05).@*CONCLUSIONS@#Early use of caffeine can shorten the duration of caffeine treatment, oxygen supply time, and length of hospital stay, with little adverse effect, in preterm infants with a gestational age of ≤31 weeks.

Effects of Shugan Hewei Decoction and active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats / 中国中药杂志

To investigate the effects of Shugan Hewei Decoction and its active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats,and preliminarily explore its possible mechanism. Male SD rats were randomly divided into blank control group,model group,fluoxetine( positive control) group,Shugan Hewei Decoction high and low dose groups,high and low dose groups of three different substance fractions. After 3 weeks' CUMS and social isolation to induce models,intragastrical administration lasted for 7 d. Behavioral experiments( sucrose consumption test,open-field test,and forced swimming test) were then performed to evaluate the depression status of rats. Several neurotransmitters in hypothalamus of rats were determined by LC-MS/MS method,including dapamine( DA),norepinephrine( NE),serotonin( 5-HT),5-indoleacetic acid( 5-HIAA),γ-aminobutyric acid( GABA),and glutamic acid( Glu). As compared with the blank control group,the sucrose consumption was reduced( P<0. 01); the total distance and the number of crossing the central area were also significantly reduced( P< 0. 01,P< 0. 01),while the resting time increased significantly( P<0. 01); the forced swimming time was significantly prolonged( P<0. 01); DA,5-HT,NE,5-HIAA and GABA levels in hypothalamus were significantly reduced( P < 0. 01),while Glue level was significantly increased( P < 0. 01) in model group. As compared with the model group,all the above indexes had changes in fluoxetine group,Shugan Hewei Decoction whole recipe groups,volatile oils group,polysaccharides group,and terpenoids group( P<0. 01 or P<0. 05). Shugan Hewei Decoction whole recipe and its active substance fractions can improve the behavior of depression model rats and may exert anti-depression effects by regulating the content of neurotransmitters in the hypothalamus.

Active substance fractions and effects of Shugan Hewei Tang on hippocampal meurotransmitters in rat model of chronic stress-induced depression / 中国中药杂志

To study the antidepressant effect of Shugan Hewei Tang on chronic stress depression model rats, and select the effective substance fractions. Several male SD rats were randomly divided into 17 groups: blank control group, model group, positive control group(fluoxetine), Shugan Hewei Tang high and low dose groups, 6 high and low dose groups of different substance fractions. After modeling for 3 weeks and administration for 1 week, the effective substance fractions were selected according to the body mass and behavioral performance of SD rats in each group; several neurotransmitters in hippocampus of rats were determined by LC-MS/MS method, including norepinephrine(NE), serotonin(5-HT), 5-indoleacetic acid(5-HIAA), r-aminobutyric acid(GABA), and glutamic acid(Glu). Behavioral results after modeling showed that as compared with the blank group, the body mass growth of the model group was significantly reduced(P<0.01); the sugar water consumption was reduced(P<0.01); the distance between the open field and the number of crossing the central area were also significantly reduced(P<0.01, P<0.01); the resting time was increased significantly(P<0.01); and the forced swimming time was significantly prolonged(P<0.01), indicating that the depression model was effective. After intragastric administration, as compared with the model group, the above detection indicators of volatile oils, total polysaccharides and terpenoid in Fluoxetine, Shugan Hewei Tang groups were all changed(P<0.05 or P<0.01). The levels of NE, 5-HT and GABA in the hippocampus of the model group were significantly lower than those in the blank group(P<0.01), and the levels of 5-HIAA and Glu were significantly increased(P<0.01). As compared with the model group, neurotransmitters of the treatment groups were changed obviously or significantly(P<0.05 or P<0.01). Shugan Hewei Tang showed obvious anti-depressant effects, and the volatile oils, total polysaccharides and terpenoids acted as the main active substances. The mechanism of anti-depression may be related to its regulation of various neurotransmitter levels in the hippocampus.

Molecular mechanism of Bupleuri Radix and Scutellariae Radix drug pair for depression based on integrative pharmacology platform of traditional Chinese medicine / 中国中药杂志

Xiaochaihu decoction is a classic prescription of traditional Chinese medicine. Modern research has proved its anti-depression effect. However, its pharmacological mechanism for anti-depression effect is difficult to be unveiled because of the complexity of compound Chinese medicines. Bupleuri Radix and Scutellariae Radix is the core drug pair of Xiaochaihu decoction. In this research, Bupleuri Radix and Scutellariae Radix were analyzed by the integrative pharmacology platform to study its molecular mechanism for anti-depression. One hundred and sixteen active ingredients were predicted, 62 for Bupleuri Radix, mainly including saikosaponins, acids, alcohols, and 54 for Scutellariae Radix, mainly including flavonoids and glycosides. Its anti-depression effect was relevant to 118 core targets, including 22 known disease targets, such as serotonin receptor(HTR2C), activating transcription factor(ATF1, ATF2), δ opioid receptor(OPRD1), μ opioid receptor (OPRM1), κ opioid receptor(OPRK1), inositol monophosphatase(IMPA1), Toll-like receptor 4 (TLR4), histamine H1 receptor(HRH1), neurotrophic factor tyrosine kinase receptor1 (NTRK1), Glycogen synthetase kinase 3β(GSK3β), etc. The antidepressant effect involved positive regulation of transcription from RNA polymerase Ⅱ promoter, transcription factor binding, cytosol, transcriptional regulation of DNA template, enzyme binding, endocrine system, nervous system, neurotrophin signaling pathway, cell growth and death, signal transduction, thyroid hormone signaling pathway and other related biological processes and metabolic pathways. This study provides a scientific evidence for further study of the anti-depression mechanism of this drug pair.