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OBJECTIVE To explore the mechanism of Kuaisong yin in the prevention and treatment of constipation. METHODS Slow transit constipation （STC） model was established with Compound difenoxylate tablet in mice and rats. Two batches of mice were divided into blank group， model group， positive control group （Maren soft capsule， 0.64 g/kg）， Kuaisong yin low-dose， medium-dose and high-dose groups （3.2， 6.4， 12.8 g/kg）， with 10 mice in each group. The effect of Kuaisong yin on constipation in mice was evaluated by intestinal propulsion experiment and defecation experiment. Rats were divided into blank group， model group， positive control group （Maren soft capsule，0.36 g/kg）， Kuaisong yin low-dose and high-dose groups （2.4， 4.8 g/kg）， with 7 or 8 rats in each group. They were given relevant medicine once a day for 1 week. The metabonomics of serum and urine of rats were analyzed by UPLC-Q-TOF-MS/MS technology. RESULTS Compared with model group， the ink propulsion rate and 5 h defecation volume of mice in Kuaisong yin high-dose group were significantly increased （P＜0.05）； the first defecation time of mice in Kuaisong yin medium-dose and high-dose groups was significantly shortened， and the quality of defecation was significantly reduced within 5 h （P＜0.05 or P＜0.01）. Serum metabonomics screened 16 compounds （such as proline， propionylcarnitine， hemolytic phosphatidylcholine， etc.） and 6 metabolic pathways （such as sphingomyelin metabolism， arginine and proline metabolism， sphingolipid biosynthesis-lactose and neolactone series）. Urine metabonomics screened 20 different metabolites （such as prostaglandin A2， L-valine， phosphatidylcholine， sphingomyelin， etc.） and 8 metabolic pathways （such as valine， leucine and isoleucine biosynthesis， sphingomyelin metabolism， pyruvate metabolism， etc.）. CONCLUSIONS Kuaisong yin can play a role in improving constipation by regulating different metabolites such as hemolytic phosphatidylcholine， phosphatidylcholine， prostaglandin A2， L-valine， proline， and regulating metabolic pathways such as multiple amino acid metabolism， sphingomyelin metabolism， etc.
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OBJECTIVE To study the mechanism of Compound zaoren granule in improving insomnia. METHODS Forty-nine mice were divided into blank group， model group， positive control group 1 （Estazolam tablets 0.5 mg/kg），control group 2 （Shumian capsule 0.6 g/kg）， Compound zaoren granule low-dose， medium-dose and high-dose groups （2.5， 5， 10 g/kg）， with 7 mice in each group. The insomnia model was established by chronic unpredictable mild stress combined with 4-chloro-DL- phenylacetic acid. The behavioral changes of mice were investigated through open field test and pentobarbital sodium synergistic hypnosis experiment， as well as the pathomorphology of mice hypothalamus tissue was observed by HE staining. The metabonomics analysis and multivariate statistical analysis of serum in mice were performed by UHPLC-Q-TOF-MS/MS， and the differential metabolites were screened out； the metabolic pathway analysis was conducted based on MetaboAnalyst 5.0 database. RESULTS Compared with blank group， the total travelling distance， the number of entering the central region and the moving distance in the central region of the model group were significantly reduced （P＜0.05）， the proportion of total rest time was significantly increased （P＜0.05）， the sleep duration of mice was significantly shortened （P＜0.05）， and hypothalamic nerve cells damaged and severely vacuolated. Compared with model group， the total travelling distance of Compound zaoren granule low-dose and medium-dose groups were increased significantly and the proportions of total rest time of those groups were decreased significantly （P＜0.05）， and the sleep duration of mice in Compound zaoren granule high-dose group was prolonged significantly （P＜0.05）； the hypothalamic nerve cells of mice in each administration group recovered to varying degrees， and the hypothalamus histiocytes of mice in the Compound zaoren granules high-dose group were closer to those in the blank group. A total of 18 differential metabolites （such as phenylalanine， taurine， norvaline， methionine） and 4 important amino acid metabolic pathways （L-phenylalanine， tyrosine and tryptophan biosynthesis； taurine and hypotaurine metabolism； L-phenylalanine metabolism； cysteine and methionine metabolism） were identified through metabolomics analysis. CONCLUSIONS Compound zaoren granules can normalize the disordered metabolism in vivo by regulating differential metabolites such as phenylalanine， taurine， and four amino acid metabolic pathways， so as to improve insomnia.
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Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity
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Objective@#To examine the association of pre-pregnancy body mass and weight gain during pregnancy with macrosomia. @*Methods@#From January 2015 to December 2015, a total of 20 477 pregnant women were recruited by probabilistic proportional scale sampling with simple randomization in Sichuan, Yunnan and Guizhou Provinces. Basic information of pregnant women, weight gain during pregnancy and weight of newborn were collected. A multiple logistic regression model was used to assess the association between the pre-pregnancy body mass and gestational weight gain indicators with macrosomia. @*Results@#20 321 mother-infant were included in the final analysis. 20 321 pregnant women were (30.09±4.10) years old and delivered at (39.20±1.29) weeks, among which 12 341 (60.73%) cases were cesarean delivery. The birth weight of 20 321 infants were (3 292.26±431.67) grams, and 970 (4.77%) were macrosomia. The multiple logistic regression model showed that after adjusting for the age of women, compared to the normal weight group in the pre-pregnancy, the overweight and obesity group elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.69−2.35) and 4.05 (95%CI: 3.05−5.39), respectively. After adjusting for the age, the pre-pregnancy BMI, delivery weeks, delivery mode and infant′s gender, compared to the weight-gain appropriate group, higher weight gain rate in the mid-pregnancy and excessive total gestational weight gain elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.66−2.39) and 1.80 (95%CI: 1.55−2.08), respectively. @*Conclusion@#The overweight before pregnancy, obesity before pregnancy, the rate of weight gain in the second trimester and the high total weight gain during pregnancy could increase the risk of macrosomia.
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Objective To explore the effects of both pre-gestational BMI and gestational weight gain (GWG) on the birth weight of neonates.Methods A total of 5 395 pregnant women were selected from the Southwest areas of China (Sichuan/Yunnan/Guizhou) and were divided into groups as pre-gestational underweight,normal weight,overweight and obesity,according to the WHO Recommendation on BMI Classification.Guidelines on Pregnancy weight were adopted from the Institute of Medicine to confirm the accuracy of GWG.Multinomial logistic regression model was used to assess the associations between pregestational BMI and GWG,on the birth weight of the neonates.Results After adjusting for related confounders,low pre-gestational BMI appeared as a risk factor for SGA (OR=1.91,95％CI:1.47-2.50),and was also associated with the decreased risk of LGA (OR=0.55,95％CI:0.47-0.66).Inadequate GWG was both associated with the increased risk of delivering SGA (OR=1.57,95％CI:1.21-2.03) and the decreased risk of LGA (OR=0.48,95％CI:0.41-0.57).Pre-gestational overweight/obesity (OR=1.85,95％CI:1.58-2.17) and excessive GWG (OR=1.87,95％CI:1.67-2.11) were both positively associated with the risks on LGA.Data from the stratified analysis indicated that inadequate GWG was positively associated with the risk of SGA among underweight or normal weight women (all P＜0.05),but not with those overweight/obese women.Conclusions Pre-gestational BMI and GWG were important influencing factors on the birth weight of neonates.Health education programs for pregnant women should be intensified and gestational weight gain should also be reasonably under control.
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Objective To explore the effects of both pre-gestational BMI and gestational weight gain (GWG) on the birth weight of neonates.Methods A total of 5 395 pregnant women were selected from the Southwest areas of China (Sichuan/Yunnan/Guizhou) and were divided into groups as pre-gestational underweight,normal weight,overweight and obesity,according to the WHO Recommendation on BMI Classification.Guidelines on Pregnancy weight were adopted from the Institute of Medicine to confirm the accuracy of GWG.Multinomial logistic regression model was used to assess the associations between pregestational BMI and GWG,on the birth weight of the neonates.Results After adjusting for related confounders,low pre-gestational BMI appeared as a risk factor for SGA (OR=1.91,95％CI:1.47-2.50),and was also associated with the decreased risk of LGA (OR=0.55,95％CI:0.47-0.66).Inadequate GWG was both associated with the increased risk of delivering SGA (OR=1.57,95％CI:1.21-2.03) and the decreased risk of LGA (OR=0.48,95％CI:0.41-0.57).Pre-gestational overweight/obesity (OR=1.85,95％CI:1.58-2.17) and excessive GWG (OR=1.87,95％CI:1.67-2.11) were both positively associated with the risks on LGA.Data from the stratified analysis indicated that inadequate GWG was positively associated with the risk of SGA among underweight or normal weight women (all P＜0.05),but not with those overweight/obese women.Conclusions Pre-gestational BMI and GWG were important influencing factors on the birth weight of neonates.Health education programs for pregnant women should be intensified and gestational weight gain should also be reasonably under control.