Humans ; Nitrogen Oxides ; poisoning ; Pulmonary Edema ; chemically induced

Objective:To investigate the absorption characteristics of matrine and glycyrrhizic acid in different intestinal segment and at various mass concentration,and explore the absorption changes of the combination of the two drugs.Methods:In situ single pass intestinal perfusion (SPIP) model was used,and the concentration changes of matrine and glycyrrhizic acid were determined by HPLC, and Kaand Peffwere calculated. Results:Matrine was absorbed in the whole of small intestine, and best in jejunum, and compared with the duodenum and ileum,the absorption had significant difference (P<0.05).The absorption at different mass concentrations had significant difference(P<0.05). The absorption of glycyrrhizic acid in small intestine was poor without significant differences in different intestinal segments and at various doses (P>0.05). After the combination of the two drugs, the absorption of matrine and glycyrrhizic acid had significant difference when compared with that of separated use(P<0.05). Conclusion:The absorption of ma-trine is dose-dependent,and with the dose increase,the absorption increases. Glycyrrhizic acid absorption does not change with mass concentration,and the absorption may be passive transport. The combination of the two drugs can improve the in vivo absorption of ma-trine and increase the concentration of glycyrrhizic acid in intestine.

Objective:To determine the equilibrium solubility and the apparent oil/water partition coefficients of nicotinate-curcu-min ester,so as to provide basis for the new formula design. Methods:Nicotinate-curcumin ester was dissolved in buffer solution with pH of 1.2-7.8. HPLC was used to detect the equilibrium solubility of nicotinate-curcumin ester in various solutions. The apparent oil/water partition coefficients in octanol-water and octanol-buffer solution system were measured by a shaking-flask method. Results:The solubility of nicotinate-curcumin ester in pH 6.8 was the highest. The apparent oil-water partition coefficients of nicotinate-curcumin ester in pH 1.2,5.8,6.5 and 7.8 were lgPapvalues within the range(lgPap=1.69-1.98) beneficial to the absorption in vivo. But in pH 2,5 and 6.8,the lgPapvalues were greater than 2 with strong lipophilicity. Conclusion:The equilibrium solubility as well as ap-parent oil/water partition coefficients of nicotinate-curcumin ester is greatly influenced by the pH value of media. In the pH value with relatively high solubility,lipophilicity is stronger,suggesting it is difficult to be absorbed by the body and needs to be further studied on dosage forms.

Objective: To explore the effect and mechanism of omega 3-polyunsaturated fatty acid(ω3-PUFA) dietary intervention on mitochondrial function of white adipose tissue in adult rats with postnatal early overfeeding. Methods: An overfed animal model by adjusting litter size was developed for the study of neonatal overfeeding. The litter size was adjusted to 3 male rats per litter(small litter, SL group) and 10 pups per litter(normal litter, NL group). After weaning(week 3), the pups were fed standard chow or ω3-PUFA diet(SL-FO) until postnatal weeks 13. Food intake, body weight, and rectal temperature of rats were measured regularly, and energy metabolism of animals was monitored in week 13. During week 3 and 13, subcutaneous adipose tissue was collected. Inguinal preadipocytes of mice were isolated and induced to differentiate, and 50 μmol/L eicosapentaenoicacid(EPA) was administered for 48 h at the late stage of differentiation. The mRNA and protein expression levels of mitochondrial related genes, mitochondrial copy number, and oxygen consumption rate of adipocytes were detected in adipose tissue and adipocytes. Results: By the 3rd week, the body weight, food intake, and fat cell area in SL group were higher than those in NL group while the body temperature was lower until to 13 weeks. By the 13th week, the O₂ consumption, CO₂ output, and heat production of rats in SL group were lower than those in NL group. Meanwhile, the expressions of mitochondrial function related genes such as uncoupling protein 1(UCP1), carnitine palmitoyltransferase 1(CPT1), SIRT1, and mitochondrial biosynthesis regulatory gene peroxisome proliferator-activated receptor coativator-1 (PGC1α) in adipose tissue by the 3rd and 13th week were significantly reduced(P<0.05). After weaning, ω3-PUFA diet significantly reduced weight gain in SL rats, increased UCP1 protein expression, restored energy metabolism level and mitochondrial function related gene expression. In vitro intervention of EPA increased the mitochondrial copy number, the mRNA and protein expression levels of mitochondrial biosynthesis and functional genes, as well as the mitochondrial basic oxygen consumption rate(P<0.05). Conclusion ω3-PUFA improves postnatal overfeeding-induced impairment of the mitochondrial function and biosynthesis of subcutaneous white adipose tissue in rats, which may be an important mechanism for fish oil diet to inhibit the early over-nutrition program and restore the thermogenic metabolism.

Objective To analyze the death status of children ≤ 5 years old in Jiaxing City from 2013 to 2017,and to provide scientific and effective measures of decreasing the children mortality and ensuring the health of children.Methods Death surveillance data of children ≤5 years old was obtained from monitoring network covering the whole city of maternal and child health information systems and the relevant maternal and child health statistics.The mortality rate,the sequence and changing trend of main death causes,prenatal health services of children ≤5 years old in Jiaxing City from 2013 to 2017were analyzed.Results From 2013 to 2017,there were 2 788 cases death of children ≤5 years old in Jiaxing City.The neonatal mortality rate (NMR),infant mortality rate (IMR),≤5 years old children mortality rate(U5MR) in Jiaxing City were 2.33‰,3.52‰ and 4.83 ‰,respectively.The mortality rates of all ages showed a declining trend year by year (x2NMR =19.641,P＜0.001;x2IMR =31.705,P ＜0.001;x2U5MR =48.294,P ＜0.001).There were significant differences in the mortality between the lower local and the migrant children (x22013 =26.16,x22014 =18.45,x22015 =27.72,x22016 =14.49,x22017=24.19;P＜0.001).The top two causes of death in children ≤ 5 years old were drowning,premature birth and low birth weight.The top two causes of death in infants and newborns were premature birth,low birth weight and other congenital anomalies.In the recent five years,49.60％ of children ≤5 years old died in the hospital.At the same time,the proportion of deaths on the way and at home was 15.64％ and 34.76％ respectively.Although there was a gap in the level of prenatal health services between local and mobile children,the gap has been declining year by year.Conclusions The key measures to decrease the mortality rate of children under 5 years old in Jiaxing City include strengthening the management of pregnancy care and high-risk pregnancy;paying attention to tertiary prevention and doing a good job in monitoring birth defects such as prenatal screening;enhancing safety education and child supervision for parents of children in 1-4 years old;reinforcing the construction of maternal and child health professional team and the technical training of newborn resuscitation techniques such as neonatal asphyxia recovery technology;intensifying the health-care and management of migrant children and improving the ability of parents to utilize child medical service.

Excessive N-acetyl-p-benzoquinone imine(NAPQI)formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen(APAP)overdose caused acute liver failure(ALF).S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity.Glutaredoxin-1(Glrx1),a glutathione-specific thioltransferase,is a primary enzyme to catalyze deglutathionylation.The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP.The Glrx1 knockout mice(Glrx1-/-)and liver-specific overexpression of Glrx1(AAV8-Glrx1)mice were produced and underwent APAP-induced ALF.Pirfenidone(PFD),a potential inducer of Glrx1,was administrated preceding APAP to assess its protective effects.Our results revealed that the hepatic total protein S-glutathionylation(PSSG)increased and the Glrx1 level reduced in mice after APAP toxicity.Glrx1-/- mice were more sensitive to APAP overdose,with higher oxidative stress and more toxic metabolites of APAP.This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p450 3a 11(Cyp3a11),which likely increased the activity of Cyp3a11.Conversely,AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11,which reduced the toxic metabolites of APAP and oxidative stress.PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress.We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose.Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.

【Objective】 To evaluate the differential miRNA expression of breast milk exosome in premature and full-term groups, and to analyze the regulatory pathways by bioinformatics, so as to provide guidance and scientific basis for the growth and development of premature infants and the prevention and treatment of related diseases. 【Methods】 From August 2020 to June 2021, breast milk samples from 13 premature (premate group) and 9 full-term infants(full-term group) in the Department of Child Health Care of the Second Affiliated Hospital of Nanjing Medical University were collected to extract exosomes. The miRNAs of two groups of breast milk exosomes were sequenced by high-throughput sequencing. According to the sequencing results, miRNA expression profiles of milk exosome were analyzed. Biological function software was used to carry out GO and KEGG pathway analysis of differential miRNA. 【Results】 The expression of miRNA in human milk exosomes was rich, especially hsa-miR-148a-3p,hsa-let-7b-5p, hsa-let-7g-5p, hsa-miR-22-3p, hsa-miR-99a-5p, hsa-miR-200, hsa-miR-146b-5p and hsa-miR-26a-5p were relatively high expressed in preterm group and full-term group. Differential expression analysis showed that compared with full-term infant breast milk, 7 miRNAs were up-regulated(log2|fold change|=2.803, 2.714, 1.632, 2.360, 1.350, 3.387, 2.137, respectively), and 5 miRNAs were down-regulated(log2|fold change|=-2.553, -2.197, -2.771, -1.395, -1.136, respectively)(|fold change>2|, P<0.05) in breast milk for preterm infants. In these differential expressed miRNAs, down-regulated miR-29b(P=0.001) and up-regulated miR-133a-3p(P=0.004) were associated with inflammation, and up-regulated miR-126-5p(P=0.021) and miR-126-3p(P=0.041) were associated with lipid metabolism. The fatty acid biosynthesis pathway was obviously enriched in preterm group. MiR-7-5p, miR-29b-3p and miR-100-5p played a role in the fatty acid synthesis pathway. 【Conclusions】 Exosomal miRNAs are rich in breast milk, and have significant differences between preterm and full-term infants′ mothers. The differentially expressed miRNA in preterm infants treast milk may be related to inflammation and promote the growth and development of preterm infants through the fatty acid biosynthesis pathway.

OBJECTIVETo evaluate the effect of individualized scalp acupuncture base on location of brain function for motor dysfunction in stroke patients.

METHODSA total of 180 patients were randomly assigned into an individualized scalp acupuncture (ISA) group, a conventional scalp acupuncture (CSA) group and a rehabilitation group, 60 cases in each one. In the ISA group, we stimulated Sishencong (EX-HN 1), motor area and balance area, matched with pre-motor area for higher muscle tension, application area and's three-needle for involuntary motion, application area for poor motor coordination, forehead five-needle for cognitive disorder, sensory area for sensory disturbance. In the CSA group, the affected Dingnieqianxiexian (MS 6), Dingniehouxiexian (MS 7) and Zhenxiapangxian (MS 14) were selected. Rehabilitation was used during needle retained in the two groups. Simple rehabilitation was used in the rehabilitation group. All the treatment was given from Monday to Friday for 4 weeks, once a day for 20 times. Eight-week follow-up was applied. The Fugl-Meyer assessment (FMA) for motor function, modified Barthel Index (MBI) were used to evaluate clinical effect.

RESULTSAfter treatment and at follow-up, FMA and MBI scores increased compared with those before treatment in the three groups（all<0.01）, with significant differences among the three groups (all<0.000 1) and better results in the ISA group compared with those in the other two groups (<0.05,<0.01) at the two time points. The FMA and MBI scores in the CSA group were higher than those in the rehabilitation group after treatment and at follow-up (all<0.05).

CONCLUSIONThe individualized scalp acupuncture can improve motor dysfunction and self-care ability of daily life for stroke patients.