Quantification of Hypsarrhythmia in Infantile Spasmatic EEG: A Large Cohort Study.

Infantile spasms (IS) is a neurological disorder causing mental and/or developmental retardation in many infants. Hypsarrhythmia is a typical symptom in the electroencephalography (EEG) signals with IS. Long-term EEG/video monitoring is most frequently employed in clinical practice for IS diagnosis, from which manual screening of hypsarrhythmia is time consuming and lack of sufficient reliability. This study aims to identify potential biomarkers for automatic IS diagnosis by quantitative analysis of the EEG signals. A large cohort of 101 IS patients and 155 healthy controls (HC) were involved. Typical hypsarrhythmia and non-hypsarrhythmia EEG signals were annotated, and normal EEG were randomly picked from the HC. Root mean square (RMS), teager energy (TE), mean frequency, sample entropy (SamEn), multi-channel SamEn, multi-scale SamEn, and nonlinear correlation coefficient were computed in each sub-band of the three EEG signals, and then compared using either a one-way ANOVA or a Kruskal-Wallis test (based on their distribution) and the receiver operating characteristic (ROC) curves. The effects of infant age on these features were also investigated. For most of the employed features, significant ( ) differences were observed between hypsarrhythmia EEG and non-hypsarrhythmia EEG or HC, which seem to increase with increased infant age. RMS and TE produce the best classification in the delta and theta bands, while entropy features yields the best performance in the gamma band. Our study suggests RMS and TE (delta and theta bands) and entropy features (gamma band) to be promising biomarkers for automatic detection of hypsarrhythmia in long-term EEG monitoring. The findings of our study indicate the feasibility of automated IS diagnosis using artificial intelligence.

Study on the Mechanism of Treating Femoral Head Necrosis with Drynariae Rhizoma Based on Network Pharmacology.

Through the network pharmacology thought, the action target of the active ingredients of Drynariae Rhizoma was predicted, and the mapping was combined with the related targets of ONFH, and the key nodes of interaction were identified for enrichment analysis, so as to comprehensively explore the pharmacological mechanism of Drynariae Rhizoma against ONFH. The main active ingredients of Drynariae Rhizoma were screened based on pharmacokinetic characteristics in pharmacokinetic database and analysis platform of TCM system (TCMSP). We used the organic small molecule bioactivity database (PubChem) and Swiss target prediction database to predict related targets based on 2D or 3D structural similarity and then mined the known ONFH therapeutic targets through the Human Mendelian Genetic Database (OMIM) and Pubmed texts. Combined with the predicted targets, String database was imported to construct the OP target interaction network diagram of bone fracture therapy. CytoNCA software was used to topology the key nodes of interaction according to relevant node parameters, and String was imported again to construct the protein interaction network diagram. Finally, biological functions and metabolic pathways of key nodes were analyzed through DAVID database. It was revealed that Drynariae Rhizoma may regulate stem cells, osteoblasts, osteoclasts, and immune cells through multiple pathways, including proliferation, differentiation, immunity, and oxidative stress. Conclusion: Pharmacological studies based on network indicate that Drynariae Rhizoma may participate in the regulation of several major signaling pathways through direct or indirect action targets and affect the proliferation and differentiation of multiple types of cells, thus playing an anti-ONFH role, which provides a scientific basis for explaining the material basis and mechanism of its anti- ONFH.

Novel CDKL5 mutations were found in patients in China: retrospective investigation in cases of CDKL5-related disorders.

OBJECTIVE: CDKL5-related disorders (CDD) is an epileptic encephalopathy resulted of gene mutations of CDKL5. This study aimed to explore the development process of CDD and to expand its mutation spectrum. METHODS: Clinic datawas collected about three infantile epileptic encephalopathy cases diagnosed at Xinhua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine. Next generation sequencing technology was used to find three de novo mutations of CDKL5. We searched published literatures about CDKL5 in pubmed and made an analysis about our clinic data and the related literatures. RESULTS: The three patients were all girls. Their average onset age of seizures was around 2 months, and all of them have intractable epileptic seizures, severe intellectual disability, and hypotension. Among them, two presented infantile spasm and high arrhythmia in EEG, and the other manifested clonic seizure and broad epileptiform discharge in EEG. Extracerebral space widening in cranial MRIs was demonstrated in two cases. Visual evoked potential was abnormal in two cases. Seizures were resistant to all kinds of antiepileptic drugs (AEDs). Gene tests showed three de novo mutations of CDKL5: one was a truncated mutation (c.2254A > T,P.R752X, stop279), which was pathogenic according to the ACMG guide, the other two were missense mutations (c.377G > T,p.Cys126Phe) and a frameshift mutation (c.362-362insG(p.Ala122GlyfsTer7), which were likely pathogenic according to the ACMG. CONCLUSIONS: All three de novo mutations are first reported. Based on the combined related literature and the manifestations observed, we diagnosed the three children as CDKL5-related disorders, and concluded that the de novo CDKL5 mutations are the reason for their epilepsy.

Comprehensive utilization of edible mushroom Auricularia auricula waste residue-Extraction, physicochemical properties of melanin and its antioxidant activity.

In order to promote the comprehensive utilization of the Auricularia auricula waste residue, the extraction process and the physicochemical properties of melanin from A. auricula waste residue were studied. Furthermore, the chemical antioxidant activity of waste residue melanin and its protective effect on cell oxidative injury induced by H2O2 were investigated. The results indicated that the ultrasonic-assisted extraction process could be used to extract the melanin from A. auricula waste residue. Melanin had a good solubility in alkali solution and exhibited a certain stability to thermal. There was no significant difference between A. auricula melanin control group and waste residue melanin on ABTS, DPPH, and hydroxyl radical scavenging activity. Waste residue melanin significantly inhibited the cell death caused by H2O2, and the cell viability was restored to 98.09 ± 5.97% when the melanin concentration was 1.6 mg/ml. Cell morphology observation confirmed that the melanin ameliorated the morphological changes of cells induced by oxidative stress.

Anti-N-methyl-D-aspartate receptor encephalitis associated with reactivated Epstein-Barr virus infection in pediatric patients: Three case reports.

RATIONALE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most frequent autoimmune encephalitis in children, and its presentation is various. The disease can be triggered by various infections. PATIENT CONCERNS: Case 1 was a 7-year-old female with the presentation of seizure, repeated fever, language disorder, and decreased muscle strength of the right limbs; Case 2 was a 7-year-old male with the manifestation of repeated emesis, headache, involuntary movement, altered personality, seizures, and cognitive impairment; Case 3 was a 2-year-old female with repeated fever, emesis, seizures, coma, and decreased muscle strength of limbs. Anti-NMDAR antibody was identified in cerebrospinal fluid (CSF) in the 3 cases, confirming the diagnosis of anti-NMDAR encephalitis. Pathogenic examinations revealed positive serum Epstein-Barr virus (EBV)-nuclear antigen and EBV-capsid antigen (CA)-IgG antibodies in the 3 cases, as well as positive EBV-early antigen (EA)-IgG antibody in CSF. Case 1 also had positive EBV-CA-IgA antibody; Case 3 also had positive EBV-CA-IgA and EBV-CA-IgG antibodies. DIAGNOSES: Anti-NMDAR antibody and EBV-EA-IgG antibody in CSF were tested positive in the 3 cases. Thus, they were diagnosed as anti-NMDAR encephalitis associated with reactivated EBV infection. INTERVENTIONS: All of the 3 cases received immunoglobulin, corticosteroid, and ganciclovir treatment. Cases 2 and 3 also received antiepileptic drugs due to repeated seizures. In addition, Case 3 also received assistant respiration, plasma exchange, and rituximab. OUTCOMES: The 3 cases were substantially recovered after treatment. Repeat CSF analysis showed decreased titer of the anti-NMDAR antibody. LESSONS: Reactivated EBV infection may trigger anti-NMDAR encephalitis in children, which has not been reported previously. Related possible virology tests should be completed while diagnosing the disease.

[Production of antioxidative exopolysaccharides of Cordyceps militaris with Vernonia amygdalina leaves in substrate].

Cordyceps militaris exopolysaccharides (EPS) have many pharmacological activities such as boosting immunity and antifatigue. To obtain EPS efficiently, we added moderate Vernonia amygdalina leaf powder as inducer to the fermentation medium to promote the production of Cordyceps militaris EPS and studied the infrared absorption spectrum and antioxidant activities of the EPS after optimization. The optimum liquid fermentation conditions were as follows: addition of Vernonia amygdalina leaf powder of 8 g/L, fermentation duration of 9 d, initial pH of 6.5, inoculation quantity of 5.0 mL. Under such a condition, the yield of Cordyceps militaris EPS reached (5.24±0.28) mg/mL, increased by 205.20% compared to the control group without adding Vernonia amygdalina leaf powder. Results of infrared analysis and antioxidant activity showed that the Vernonia amygdalina leaves had little effect on the structure and activities of Cordyceps militaris EPS. The results of this research suggest that Vernonia amygdalina leaf can enhance the production of Cordyceps militaris EPS effectively, and provides a novel method for efficient production of EPS in Cordyceps militaris.

Characterization of natural melanin from Auricularia auricula and its hepatoprotective effect on acute alcohol liver injury in mice.

This study characterized the natural melanin from Auricularia auricula and investigated its hepatoprotective effect on mice with acute alcoholic liver injury. The characterization of the melanin was analyzed based on elemental analysis, gel permeation chromatography (GPC), UV-visible spectroscopy (UV-visible), infrared spectrum (IR) and nuclear magnetic resonance spectra (NMR). To determine the liver protective effect of Auricularia auricula melanin, mice were administered with the melanin once daily for 3 weeks before ethanol induced liver injury. Biochemical parameters of liver function, histopathological sections, mRNA and protein expression of antioxidant enzyme were compared between mice with or without the melanin administered. Results showed that A. auricula melanin was a eumelanin and the average molecular weight was 48.99 kDa. The melanin can protect the mice from ethanol-induced liver injury by extending the duration of the righting reflex, and shortening the duration of the recovery. The liver index, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GT) and liver malondialdehyde (MDA) levels in mice treated with the melanin were significantly decreased. At the same time, the levels of liver alcohol dehydrogenase (ADH), and antioxidase such as catalase (CAT), and superoxide dismutase (SOD) were increased. Its protective effect may be related to the activation of nuclear factor E2-related factor 2 (Nrf2) and its downstream antioxidant enzymes such as glutamate cysteine ligase catalytic (GCLC), glutamate cysteine ligase modifier (GCLM), and NADP(H) quinine oxidoreductase 1 (NQO-1). These results suggested that A. auricula melanin may be an effective strategy to alleviate alcohol-induced liver damage.

Purification and characterization of Inonotus hispidus exopolysaccharide and its protective effect on acute alcoholic liver injury in mice.

This study characterized the Inonotus hispidus extracellular exopolysaccharide (IHEPS) from fermentation broth and investigated its liver protective effect on acute alcoholic liver injury in mice. The characterization of IHEPS was analyzed by HPLC, UV-vis and FT-IR. To determine the liver protective effect of IHEPS, mice were administered with IHEPS once daily for 3 weeks, before ethanol induced acute alcoholic liver injury. Biochemical parameters of liver function, histopathological sections, mRNA and protein expression of related antioxidant enzymes were compared between with or without IHEPS administrated mice. As a result, IHEPS could extend the duration of righting reflex, shorten the durations of the recovery, and decrease the liver index in acute alcoholic liver mice. At the same time, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) levels were decreased in IHEPS mice. Moreover, increased alcohol dehydrogenase (ADH), catalase (CAT) and superoxide dismutase (SOD) levels were also found in IHEPS mice. Furthermore, IHEPS activated Nrf2 signaling pathway and increased the expression of downstream related antioxidant enzymes, such as NQO1, CAT and Cu-Zn SOD.

Extraction, characterization and antioxidant activity analysis of the polysaccharide from the solid-state fermentation substrate of Inonotus hispidus.

A polysaccharide from Inonotus hispidus was prepared by solid-state fermentation (SSF), and an efficient ultrasound-assisted extraction method was used to optimize the extraction process of Inonotus hispidus solid-state fermentation polysaccharide (IHSFP). The optimal extraction parameters were as follows: solid-liquid ratio of 1:40, ultrasound time of 34 min, ultrasound power of 350 W and ultrasound temperature of 70 °C. The yield of IHSFP was 51.06 ±â€¯0.34% under the optimal conditions. Two types of polysaccharide fractions (IHSFP-1 and IHSFP-2) were isolated by DEAE-52 and Sephadex G-200 columns. IHSFP-2 had stronger antioxidant activity than IHSFP-1, and it can reduce H2O2-induced oxidative damage to cells in vitro. Therefore, the properties of IHSFP-2 were further characterized. The results showed that the molecular weight of IHSFP-2 was 14.44 kDa, it was composed of glucose (Glc), mannose (Man), galactose (Gal), glucuronic acid (GlcUA), galactosamine (GalN), arabinose (Ara) and ribose (Rib), and the contents of these monosaccharides were 51%, 21%, 20%, 3%, 2%, 2% and 1%, respectively. The results of this study may contribute to the efficient production of the polysaccharide of Inonotus hispidus, and provide new ideas for its application in functional foods and cosmetics.

Characterization of the physicochemical properties and extraction optimization of natural melanin from Inonotus hispidus mushroom.

In this study, solid-state fermentation was used to produce Inonotus hispidus melanin (IH melanin). Its physicochemical properties were characterized, and ultrasonic-assisted extraction was used to optimize its extraction process. Characterization techniques like elemental analysis and so on were used to identify melanin. The solubility, stability, and antioxidant activity were also measured. Furthermore, the extraction process of IH melanin was optimized. The results showed that the pigment could be defined as dihydroxy phenylalanine (DOPA)-melanin, it displayed irregular spherical and ellipsoidal structures with average size of 89.33 nm. Melanin has a specific stability and shows antioxidant activity. The optimal extraction parameters of melanin were a NaOH concentration of 0.56 mol/L, solid-liquid ratio of 1:50, ultrasonic power of 300 W, extraction temperature of 70 °C, and ultrasonic time of 70 min. This study was the first time that IH melanin was obtained. The results may be applied to health food or food additives.

Associations between maternal lipid profile and pregnancy complications and perinatal outcomes: a population-based study from China.

BACKGROUND: Dyslipidemia in pregnancy are associated with gestational diabetes mellitus (GDM), preeclampsia, preterm birth and other adverse outcomes, which has been extensively studied in western countries. However, similar studies have rarely been conducted in Asian countries. Our study was aimed at investigating the associations between maternal dyslipidemia and adverse pregnancy outcomes among Chinese population. METHODS: Data were derived from 934 pairs of non-diabetic mothers and neonates between 2010 and 2011. Serum blood samples were assayed for fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) concentrations during the first, second and third trimesters. The present study explored the associations between maternal lipid profile and pregnancy complications and perinatal outcomes. The pregnancy complications included GDM, preeclampsia and intrahepatic cholestasis of pregnancy (ICP); the perinatal outcomes included preterm birth, small/large for gestational age (SGA/LGA) infants and macrosomia. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated and adjusted via stepwise logistic regression analysis. Optimal cut-off points were determined by ROC curve analysis. RESULTS: After adjustments for confounders, every unit elevation in third-trimester TG concentration was associated with increased risk for GDM (OR = 1.37, 95% CI: 1.18-1.58), preeclampsia (OR = 1.50, 95% CI: 1.16-1.93), ICP (OR = 1.28, 95% CI: 1.09-1.51), LGA (OR = 1.13, 95% CI: 1.02-1.26), macrosomia (OR = 1.19, 95% CI: 1.02-1.39) and decreased risk for SGA (OR = 0.63, 95% CI: 0.40-0.99); every unit increase in HDL-C concentration was associated with decreased risk for GDM and macrosomia, especially during the second trimester (GDM: OR = 0.10, 95% CI: 0.03-0.31; macrosomia: OR = 0.25, 95% CI: 0.09-0.73). The optimal cut-off points for third-trimester TG predicting GDM, preeclampsia, ICP, LGA and SGA were separately ≥ 3.871, 3.528, 3.177, 3.534 and ≤ 2.530 mmol/L. The optimal cut-off points for third-trimester HDL-C identifying GDM, macrosomia and SGA were respectively ≤ 1.712, 1.817 and ≥ 2.238 mmol/L. CONCLUSIONS: Among Chinese population, maternal high TG in late pregnancy was independently associated with increased risk of GDM, preeclampsia, ICP, LGA, macrosomia and decreased risk of SGA. Relative low maternal HDL-C during pregnancy was significantly associated with increased risk of GDM and macrosomia; whereas relative high HDL-C was a protective factor for both of them.

Cord blood C-peptide, insulin, HbA1c, and lipids levels in small- and large-for-gestational-age newborns.

BACKGROUND: Small- and large-for-gestational-age (SGA, LGA) newborns are associated with metabolic syndrome in their later life. Cord blood C-peptide, insulin, glycosylated hemoglobin (HbA1c), and lipids levels may be altered in SGA and LGA newborns; however, the results are conflicting. Therefore, this study aimed to determine the effect of cord blood markers on SGA and LGA newborns. MATERIAL AND METHODS: This was a prospective cohort study and included 2873 term newborns of non-diabetic women. Among these newborns, 83 (2.9%) were SGA, 2236 (77.8%) were appropriate-for-gestational-age (AGA), and 554 (19.3%) were LGA newborns. Cord blood C-peptide, insulin, HbA1c, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. The chi-square, Kruskal-Wallis, and Mann-Whitney tests were used to analyze categorical variables and continuous variables, respectively. Multinomial logistic regression analysis was used to determine the independent effect of these variables on SGA and LGA newborns. RESULTS: Cord serum TG level was significantly higher in the SGA group than in AGA and LGA groups (p<0.05). The LGA group had significantly higher cord serum insulin level than AGA and SGA groups (p<0.05). After adjustment for confounding variables, including maternal age, parity, pre-pregnancy body mass index (BMI), education, annual household income, pregnancy-induced hypertension (PIH), mode of delivery, and newborn sex, high TG and insulin levels remained significantly associated with SGA and LGA newborns, respectively (p<0.05). CONCLUSIONS: High cord serum TG and insulin levels are independently associated with SGA and LGA newborns, respectively.

Effect of maternal lipid profile, C-peptide, insulin, and HBA1c levels during late pregnancy on large-for-gestational age newborns.

BACKGROUND: Large-for-gestational age (LGA) newborns can increase the risk of metabolic syndrome. Previous studies have shown that the levels of maternal blood lipids, connecting peptide (C-peptide), insulin and glycosylated hemoglobin (HbA1c) were significantly different between LGA and appropriate-for-gestational age (AGA) newborns. This study aimed to determine the effect of the levels of maternal lipids, C-peptide, insulin, and HbA1c during late pregnancy on LGA newborns. METHODS: This study comprised 2790 non-diabetic women in late pregnancy. Among their newborns, 2236 (80.1%) newborns were AGA, and 554 (19.9%) newborns were LGA. Maternal and neonatal characteristics were obtained from questionnaires and their case records. The levels of maternal fasting serum apolipoprotein A1 (ApoA1), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), C-peptide, insulin and blood HbA1c were measured. The chi-square and Mann-Whitney U test were used to analyze categorical variables and continuous variables between the AGA and LGA groups, respectively. Binary logistic regression analysis was made to determine the independent risk factors for LGA newborns. RESULTS: Maternal TG, C-peptide, insulin and HbA1c levels were significantly higher in the LGA group than in the AGA group (P<0.05). The LGA group had significantly lower levels of maternal TC, HDL-C and LDL-C than the AGA group (P<0.05). After adjustment for confounding variables, including maternal age, pre-pregnancy body mass index, education, smoking, annual household income, amniotic fluid volume, gestational hypertension, newborn gender and gestational age at blood collection, high maternal TG levels remained significantly associated with LGA newborns (P<0.05). CONCLUSION: High maternal TG level during late pregnancy is significantly associated with LGA newborns.