Urine metabolic profiles in paediatric asthma.

BACKGROUND AND OBJECTIVE: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology. METHODS: Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes. RESULTS: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma. CONCLUSION: Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.

Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome.

INTRODUCTION: Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring in the first 3 months of life. The most common causes of neonatal cholestasis are infantile hepatitis syndrome (IHS) and biliary atresia (BA). The clinical manifestations of the two diseases are too similar to distinguish them. However, early detection is very important in improving the clinical outcome of BA. Currently, a liver biopsy is the only proven and effective method used to differentially diagnose these two similar diseases in the clinic. However, this method is invasive. Therefore, sensitive and non-invasive biomarkers are needed to effectively differentiate between BA and IHS. We hypothesized that urinary metabolomics can produce unique metabolite profiles for BA and IHS. OBJECTIVES: The aim of this study was to characterize urinary metabolomic profiles in infants with BA and IHS, and to identify differences among infants with BA, IHS, and normal controls (NC). METHODS: Urine samples along with patient characteristics were obtained from 25 BA, 38 IHS, and 38 NC infants. A non-targeted gas chromatography-mass spectrometry (GC-MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis (OPLS-DA) to explore the metabolomic profiles of BA, IHS, and NC infants. RESULTS: In total, 41 differentially expressed metabolites between BA vs. NC, IHS vs. NC, and BA vs. IHS were identified. N-acetyl-D-mannosamine and alpha-aminoadipic acid were found to be highly accurate at distinguishing between BA and IHS. CONCLUSIONS: BA and IHS infants have specific urinary metabolomic profiles. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be used to discriminate BA from IHS.

[Metabonomics of Syndrome Markers in Infantile Bronchial Asthma Episode].

Objective To analyze urinary metabolites of bronchial asthma children patients with phlegm-heat obstructing Fei syndrome (PHOFS) and non-PHOFS using gas chromatography-mass spec- trometry/mass spectrometer ( GC-MS/MS) , thus performing research on syndrome markers. Methods Totally 44 bronchial asthma children patients with PHOFS and non-PHOFS in onset of asthma were recrui- ted. Another 29 healthy children were also recruited. Their urine samples were analyzed by GC-MS/MS. The profiles were analyzed using orthogonal partial least squares-discriminant analysis (OPLS-DA) , vari- able importance in the projection (VIP) , and non-parametric test to determine intergroup differential metabolites. Abnormal metabolic pathways were determined by Metaboanalyst. Results Compared with the health control group, contents of fourteen substances like inositol, uric acid, stearic acid, and so on de- creased, and mino-malonic acid content increased in asthma episode children (P <0. 05). The process was mainly involved in 5 metabolic pathways such as lysine degradation and biosynthesis, pyruvate me- tabolism, and so on. Compared with the non-PHOFS group in bronchial asthma episode, contents of nine substances like oxalic acid, L-threonine, pyrimidine, and so on decreased in the PHOFS group (P < 0. 05). The process was mainly involved in 5 metabolic pathways such as pentose phosphate pathway, inositol phosphate metabolism, and so on. Conclusions Urinary metabolites are different in infantile bronchial asthma episode and healthy children. Metabolic biomarkers and pathways exist in different syn- dromes in bronchial asthma episode.

Economic burden and its associated factors of hospitalized patients infected with A (H7N9) virus: a retrospective study in Eastern China, 2013-2014.

BACKGROUND: H7N9 continues to cause human infections and remains a pandemic concern. Understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. However, there are limited data on such impacts. METHODS: Hospitalized laboratory-confirmed H7N9 patients or their families in Jiangsu Province of China were interviewed. Patients' direct medical costs of hospitalization were derived from their hospital bills. A generalized linear model was employed to estimate the mean direct medical costs of patients with different characteristics. RESULTS: The mean direct cost of hospitalization for H7N9 was estimated to be ¥ 71 060 (95 % CI, 48 180-104 820), i.e., US$ 10 996 (95 % CI, 7 455-16 220), and was ¥12 060 (US$ 1 861), ¥136 120 (US$ 21 001) and ¥218 610 (US$ 33 728) for those who had mild or severe symptoms or who died, respectively. The principal components of the total fees differed among patients with different disease severity, although medication fees were always the largest contributors. Disease severity, proportion of reimbursement and family member monthly average income were identified as the key factors that contributed to a patient's direct medical cost of hospitalization. CONCLUSIONS: The direct medical costs of hospitalized patients with H7N9 are significant, and far surpass the annual per capita income of Jiangsu Province, China. The influencing factors identified should be taken into account when developing related health insurance policies and making health resource allocation. TRIAL REGISTRATION: Not applicable. This is a survey study with no health care intervention implemented on human participants.

[Regulation of Jinxin Oral Liquid for the expression of negative regulatory factor of TLR3 signaling pathway SOCS1 in RSV infected BALB/c mice].

OBJECTIVE: To investigate the regulation trend of Jinxin Oral Liquid (JXOL) on the expression of negative regulatory factor of TLR3 signaling pathway SOCS1 in the lung tissue of RSV infected BALB/c mice at different time points. METHODS: Totally 75 BALB/c mice were randomly divided into 5 groups, i.e., the normal control group, the model group, the ribavirin group, the high dose JXOL group, and the equivalent dose JXOL group, 15 in each group. Each group had 3 intervention ways (I, II, and III) with 5 mice treated in each group. BALB/c mice were nasally infected with respiratory syncytial virus (RSV), and treated by different intervention ways. After intervention, mice were killed and their lung tissues were sampled, mRNA expression levels of RSV-M, SOCS1, and IFN-ß were detected by Real time PCR. The expression of SOCSl at the protein level was detected by Western blot. RESULTS: Compared with the normal control group, the mRNA expression level of SOCS1 and IFN-ß, and the protein expression level of SOCS1 increased significantly in the model group intervened by intervention I and II (all P < 0.01), but the mRNA expression level of IFN-ß decreased significantly in model group intervened by intervention III (P < 0.01). Compared with the model group, the mRNA expression level of RSV-M all significantly decreased in the high dose JXOL group and the equivalent dose JXOL group intervened by 3 intervention ways (all P < 0.01). The mRNA expression level of SOCS1 significantly decreased in the high dose JXOL group intervened by intervention I and III and the equivalent dose JXOL group intervened by 3 intervention ways (all P < 0.01). The mRNA expression level of IFN-ß significantly decreased in the high dose JXOL group intervened by intervention I and II and the equivalent dose JXOL group intervened by intervention I (all P < 0.01), while it significantly increased in the high dose JXOL group intervened by intervention III and the equivalent dose JXOL group intervened by intervention III (all P < 0.01). The protein expression level of SOCS1 significantly decreased in the high dose JXOL group intervened by intervention I and the equivalent dose JXOL group intervened by 3 intervention ways (all P < 0.01), while it significantly increased in the high dose JXOL group intervened by intervention III (all P < 0.01). Compared with the high dose JXOL group, the mRNA expression level of RSV-M decreased significantly in the equivalent dose JXOL group intervened by intervention I and II (P < 0.01). The mRNA expression level of SOCS1 and IFN-ß decreased significantly in the equivalent dose JXOL group intervened by intervention I (P < 0.01), but the mRNA expression level of IFN-ß increased significantly in the equivalent dose JXOL group intervened by intervention II and III (all P < 0.01). The protein expression level of SOCS1 decreased significantly in the equivalent dose JXOL group intervened by 3 intervention ways (all P < 0.01). CONCLUSIONS: JXOL could inhibit the expression of SOCS1 in the lung tissue of RSV infected BALB/c mice at different time points. Its regulatory effect might be associated with promoting the expression of interferon type I and further fighting against RSV.

Immunogenicity, safety, and lot consistency of a novel inactivated enterovirus 71 vaccine in Chinese children aged 6 to 59 months.

The determination of lot-to-lot consistency in the manufacturing process is a mandatory step in the clinical development of the novel enterovirus 71 (EV71) vaccine. A phase III, randomized, placebo-controlled, double-blind trial assessed the lot consistency, immunogenicity, and safety of the EV71 vaccine in children aged 6 to 59 months. Healthy children (n = 1,400) received one of three lots of the EV71 vaccine containing 400 U of EV71 antigen or a placebo at days 0 and 28. Blood samples were collected before dose 1 and at 28 days after dose 2 (day 56) for an anti-EV71 neutralizing antibody (NTAb) assay. The geometric mean titer (GMT) and the seropositivity rates (with titers of ≥1:8) were compared at day 56. After each dose, the solicited injection site and general adverse events (AEs) were recorded for 7 days, and unsolicited AEs were recorded for 28 days. At day 56, the seropositivity rates ranged from 99.7% to 100% for the vaccine groups. The NTAb GMTs for the vaccine were 140.3 (95% confidence interval [CI], 117.8 to 167.1), 141.5 (95% CI, 118.0 to 169.6), and 146.6 (95% CI, 122.5 to 175.3). The two-sided 95% CI of the log difference in GMTs between the pairs of lots were between -0.176 and 0.176, therefore meeting the predefined equivalence criteria. The percentages of subjects reporting any injection site AEs, general AEs, or serious AEs were similar across the four vaccination groups. In conclusion, the demonstration of consistency between the manufacturing lots confirms for the purposes of clinical development the reliability of the EV71 vaccine production process. (This study has been registered at ClinicalTrials.gov under registration no. NCT01636245.).

[Relevant pathogenesis of heat and phlegm in infantile viral pneumonia: an analysis by association rules].

OBJECTIVE: To study the application of association rules in Chinese medical pathogeneses and pathologies of heat and phlegm in infantile viral pneumonia. METHODS: Association rules were applied to analyze dynamic changes of heat and phlegm correlated symptoms and signs in 297 infants with respiratory syncytial virus (RSV) pneumonia, thus understanding its evolution or pathogenesis. RESULTS: Heat and phlegm co-exist in infantile viral pneumonia. In their relationship, heat was more likely to affect phlegm, but phlegm was less likely to affect heat. Under the intervention of drugs, the possibility of heat induced by phlegm was gradually reduced. But the possibility of phlegm induced by heat was not obvious as time went by. CONCLUSIONS: Heat and phlegm have a close relationship in the pathogenesis of infantile viral pneumonia. The intervention of drugs could reduce the pathologic evolution of phlegm causing heat. However, it has little effect on the pathologic evolution of heat causing phlegm.

[Epidemiological characteristics and temporal-spatial clustering analysis on hand-foot-mouth disease in Jiangsu province, 2009 - 2011].

OBJECTIVE: To analyze the epidemic characteristics of hand-foot-mouth disease (HFMD) in Jiangsu province. METHODS: We downloaded the case-data of HFMD in Jiangsu province during 2009 - 2011 from the Chinese National Notifiable Infectious Disease Reporting System, and made a comprehensive analysis on the epidemiological features of it with descriptive epidemiological methods and retrospective space-time permutation scan statistics. RESULTS: A total of 285 414 cases were reported in Jiangsu, from 2009 to 2011, with an annual incidence of 122.66 per 100 000. There were 3686 severe cases in the 3 years a cumulatively, accounting for 1.29% of the total. Proportion of the cases being 5 years old or even younger was 93.64%. Scatteredly living children accounted for 64.08% of the total cases and 78.65% of the severe cases, respectively. The epidemics of HFMD were visible in each city of Jiangsu province, with a lowest annual incidence rate of 44.02 per 100 000 and a highest one up to 202.90 per 100 000. Regions as Suzhou, Nanjing, Wuxi had the highest incidence in the province, with cases in these three areas occupying almost 40% of all. The numbers of severe cases in Suqian and in Yancheng cities increased by 339.22% and 328.33% in 2011 compared to in 2010, respectively, and the rates of increase in these two cities were much higher than those in the other regions. Two peaks of incidence were observed every year, with the highest occurring between April and June and the second occurring in November. The spatial-temporal distribution of HFMD was not random in Jiangsu province, from 2009 to 2011. Clusters for general cases in August and 7 clusters for severe cases were detected, respectively. 12 359 cases of HFMD were laboratory confirmed in the said 3 years, including 10 414 common cases and 1945 severe cases. EV71 and CoxA16 accounted for 43.49% and 37.07% of common cases, respectively. In terms of the severe cases, the ratios were 80.82% and 5.96%, respectively. CONCLUSION: HFMD was highly endemic in Jiangsu province, and the situation of prevention and control for it is still grim. Scatteredly living children of 5 years old or younger were the major population at risk, and the epidemic in different regions and seasons was different. EV71 and CoxA16 were the major etiologic agents, but the etiologic constitute showed seasonal changes.

[Study on fibrolytic and hypotensive activity of earthworm homogenate of ultrafiltration separation from enzymolysis].

OBJECTIVE: To study the fibrolytic and hypotensive activity of earthworm homogenate of ultrafiltration separation from simulated enzymolysis of gastrointestinal tract system. METHODS: The before and after enzymolysis homogenate of fresh earthworm was seperated with different pore size PVDF ultrafiltration membrane and its fibrolytic and hypotensive activity was assayed. RESULTS: The fibrolytic activity of the total homogenate after enzymolysis overall changed little, but decreased in the the site of higher molecular weight and increased in the lower site of molecular weight; The ACE inhibitory activity improved, especially in the filtrate of the MW 4000 membrane. CONCLUSION: The fibrolytic activity of earthworm homogenate was not reduced by the digestive simulated enzymolysis, and the retention site of MW 10 000 membrane have more fibrolytic activity; The hypotensive activity of earthworm homogenate is enhanced by the digestive simulated enzymolysis. So the stronger activity could be obtained from enzymolysis.