[Clinical characteristics and ketogenic diet therapy of glucose transporter type 1 deficiency syndrome in children: a multicenter clinical study].

Objective: To explore the clinical characteristics of pediatric glucose transporter type 1 deficiency syndrome (GLUT1 DS), evaluate the efficacy and safety of ketogenic diet therapy (KDT). Methods: Clinical data of 19 children with GLUT1 DS admitted to Children's Hospital of Fudan University, Tianjin Children's Hospital, Shenzhen Children's Hospital, Children's Hospital of Nanjing Medical University and Jiangxi Provincial Children's Hospital between 2015 and 2019 were collected retrospectively. The first onset symptom, main clinical manifestations, cerebrospinal fluid features and genetic testing results of patients were summarized, the efficacy and safety of ketogenic diet treatment were analyzed. Results: Among the 19 cases, 13 were males and 6 females. The age of onset was 11.0 (1.5-45.0) months,the age of diagnosis was 54.0 (2.8-132.0) months. Epilepsy was the first onset symptom of 13 cases. Different forms of tonic-clonic seizures were the most common types of epilepsy (7 cases with generalized tonic-clonic seizures, 5 cases with focal tonic or clonic seizures, 4 cases with generalized tonic seizures). Antiepileptic drugs were effective in 4 cases. Paroxysmal motor dysfunction was present in 12 cases and ataxia was the most common one. All patients had different degrees of psychomotor retardation. Among 17 patients received cerebrospinal fluid examination, cerebrospinal fluid (CSF) glucose level was lower than 2.2 mmol/L and CSF glucose/glycemic index was<0.45 in 16 cases, only 1 case presented normal CSF glucose level (2.3 mmol/L) and normal CSF glucose/glycemic index(0.47). SLC2A1 gene mutations were found in 16 patients, missense, frameshift and nonsense mutations were the common types with 5 cases, 5 cases and 3 cases respectively. All 19 patients were treated with ketogenic diet, which was effective in 18 cases in seizure control, 11 cases in dyskinesia improvement and 18 cases in cognitive function improvement. No serious side effects were reported in any stage of KDT. Conclusions: The diagnosis of GLUT1 DS is often late. It is necessary to improve the early recognition of the disease and perform CSF glucose detection and genetic testing as early as possible. The KDT is an effective and safe treatment for GLUT1 DS, but a small number of patients have not response to diet therapy.

Lipopolysaccharide-stimulated bone marrow mesenchymal stem cells-derived exosomes inhibit H2O2-induced cardiomyocyte inflammation and oxidative stress via regulating miR-181a-5p/ATF2 axis.

OBJECTIVE: Myocardial infarction (MI) is a cardiovascular disease that seriously endangers human health. Exosomes secreted by stem cells have big potential for the treatment of many diseases. The purpose of this study was to study the therapeutic effects of exosomes derived from lipopolysaccharide (LPS)-stimulated bone marrow mesenchymal stem cells (BMSCs) on MI. PATIENTS AND METHODS: The surface markers of BMSCs were detected by Western blot. After BMSCs were stimulated with LPS for 2 days, the exosomes secreted by BMSCs were extracted and observed by transmission electron microscopy (TEM), and their specific surface markers were detected by Western blot. H9c2 cells were co-cultured with exosomes for 24 hours, and then, treated with H2O2 for 4 hours. Next, H9c2 cells were transfected with miRNA-181a-5p mimic (MIM) or negative control (NC). Inflammation and oxidative stress of H9c2 cells were detected by Western blot, cell staining, reactive oxygen species (ROS) quantification, and SOD activity assay. At last, miR-181a-5p expression in BMSCs, exosomes, and H9c2 cells was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). RESULTS: The results revealed that the expression of miR-181a-5p was increased in LPS-stimulated BMSCs (L-BMSC) and in their secreted exosomes. Besides, the expressions of TNF-α and IL-1ß were decreased, while those of SOD1 and SOD2 were increased in H9c2 cells co-cultured with exosomes secreted by LPS-stimulated BMSCs (L-EXO) and transfected with MIM. Moreover, the fluorescence intensity of IL-1ß immunofluorescence was decreased in H9c2 cells co-cultured with L-EXO or transfected with MIM. The level of ROS was also decreased in H9c2 cells co-cultured with L-EXO or transfected with MIM. Furthermore, miR-181a-5p was found to target ATF2 through target gene prediction databases and Western blot and Dual-Luciferase reporter assays. CONCLUSIONS: LPS stimulation can increase the expression of miR-181a-5p in BMSCs, and miR-181a-5p inhibits myocardial inflammation and oxidative stress by targeting ATF2.

First Measurement of the g Factor in the Chiral Band: The Case of the

The g factor of the 56 ns half-life isomeric state in ^{128}Cs has been measured using the time-differential perturbed angular distribution method. This state is the bandhead of the positive-parity chiral rotational band, which emerges when an unpaired proton, an unpaired neutron hole, and an even-even core are coupled such that their angular momentum vectors are aplanar (chiral configuration). g-factor measurements can give important information on the relative orientation of the three angular momentum vectors. The measured g factor g=+0.59(1) shows that there is an important contribution of the core rotation in the total angular momentum of the isomeric state. Moreover, a quantitative theoretical analysis supports the conclusion that the three angular momentum vectors lie almost in one plane, which suggests that the chiral configuration in ^{128}Cs demonstrated in previous works by characteristic patterns of electromagnetic transitions appears only above some value of the total nuclear spin.

Improving neural network prediction of effluent from biological wastewater treatment plant of industrial park using fuzzy learning approach.

Three types of adaptive network-based fuzzy inference system (ANFIS) in which the online monitoring parameters served as the input variable were employed to predict suspended solids (SS(eff)), chemical oxygen demand (COD(eff)), and pH(eff) in the effluent from a biological wastewater treatment plant in industrial park. Artificial neural network (ANN) was also used for comparison. The results indicated that ANFIS statistically outperforms ANN in terms of effluent prediction. When predicting, the minimum mean absolute percentage errors of 2.90, 2.54 and 0.36% for SS(eff), COD(eff) and pH(eff) could be achieved using ANFIS. The maximum values of correlation coefficient for SS(eff), COD(eff), and pH(eff) were 0.97, 0.95, and 0.98, respectively. The minimum mean square errors of 0.21, 1.41 and 0.00, and the minimum root mean square errors of 0.46, 1.19 and 0.04 for SS(eff), COD(eff), and pH(eff) could also be achieved.

Comparisons of grey and neural network prediction of industrial park wastewater effluent using influent quality and online monitoring parameters.

In this study, Grey model (GM) and artificial neural network (ANN) were employed to predict suspended solids (SSeff) and chemical oxygen demand (CODeff) in the effluent from a wastewater treatment plant in industrial park of Taiwan. When constructing model or predicting, the influent quality or online monitoring parameters were adopted as the input variables. ANN was also adopted for comparison. The results indicated that the minimum MAPEs of 16.13 and 9.85% for SSeff and CODeff could be achieved using GMs when online monitoring parameters were taken as the input variables. Although a good fitness could be achieved using ANN, they required a large quantity of data. Contrarily, GM only required a small amount of data (at least four data) and the prediction results were even better than those of ANN. Therefore, GM could be applied successfully in predicting effluent when the information was not sufficient. The results also indicated that these simple online monitoring parameters could be applied on prediction of effluent quality well.

Phase II trial of a 2-h infusion of gemcitabine plus carboplatin as first-line chemotherapy for advanced non-small-cell lung cancer.

PURPOSE: To evaluate the efficacy and safety of the combination of using gemcitabine as a rate infusion of 10 mg/m(2) per min with carboplatin in front-line chemonaive patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-four chemonaive patients with stage IIIB or IV NSCLC have been included, 44 males and 10 females, with a median age 63 years (range 19-75). Thirty-two (59%) patients had adenocarcinoma, 13 (24%) squamous cell, 1 (2%) large cell carcinoma and 8 (15%) others. Eight (15%) had stage IIIB and 46 (85%) stage IV. Treatment was consisted of 1,200 mg/m(2) gemcitabine given as a 2-h continuous infusion (10 mg/m(2) per min) on days 1 and 8 of each cycle an AUC 5 carboplatin as on day 1, repeating each cycle for every 21 days. A total of 223 chemotherapy cycles were administered, with a median of four cycles per patient (range 1-6), and 15 (28%) patients received all six cycles. RESULTS: Of the 54 patients enrolled, all were evaluated for toxicity and 51 assessed for response. The overall response rate was 41% (95% confidence interval, 28-57%) with complete and partial responses of 4 and 37%, respectively. The median time to disease progression was 5.0 months (95% CI, 3.7-6.3 months), and median overall survival time was 11.5 months (95% CI, 9.9-13.1 months). One-year survival was 42%. The main grade 3-4 toxicity (according to the WHO scale) consisted of neutropenia (56%) and thrombocytopenia (57%). Patients were required platelet transfusion in 27 cycles (12%) and hematopoietic growth factors support care in 56 (25%) cycles. No bleeding episodes were recorded. Grade 3 nausea/vomiting occurred in 6% and grade 1-2 skin rash occurred in 43%. CONCLUSIONS: Prolonged gemcitabine infusion combined with carboplatin is manageable and tolerated, and its efficacy is similar to that of other chemotherapeutic schemes used for NSCLC treatment.

A pilot study on the changes of event-related potentials in school-aged children with iron deficiency anaemia.

Event-related potentials (ERP) were assessed in 70 school-aged children with a diagnosis of asymptomatic iron deficiency anaemia (IDA), based on low haemoglobin and either low serum ferritin or high free erythrocyte protoporphyrin levels. The IDA subjects were randomized into treatment and placebo groups of 35 cases each, and compared with a normal control group of 30 age- and gender-matched healthy subjects without iron deficiency. Further haematological and ERP assessment was carried out after 3 months, during which time the active group received iron supplementation with 10 mg ferrous sulphate, together with vitamin C, malic acid and folic acid. Pre-treatment, both IDA groups had prolonged P300 latencies in comparison with the non-IDA controls (p<0.01). The proportion of cases with distorted wave appearance was more than twice as high in the IDA groups as in the non-IDA controls, although intergroup differences did not reach statistical significance. After treatment, the active treatment IDA group showed a significant increase in haemoglobin levels and shortening in P300 latencies. After treatment, neither value was statistically different from non-IDA controls. There was a decrease in the number of cases with abnormal waveforms in the active treatment group, compared with an increase in the number within the placebo group (P = 0.002). Testing of ERP shows promise as a non-invasive, sensitive and objective marker for assessing cognitive impairment in children with IDA.

[Angiotensin II type 2 receptor gene deletion does not affect renin-angiotensin system].

It has been postulated that Angiotensin II type 2 receptor (AT2) functionally antagonizes type 1 (AT1) receptor. In the present study, we investigated whether gene deletion of AT2 receptor causes the compensatory chaos of renin-angiotensin system in mice. It was shown that the concentrations of Angiotensin II in plasma and kidney tissues and the expressions of renin and AT1A receptor in the AT2 gene null mice were unchanged, as compared with those in AT2 wild-type mice. This result suggests that gene deletion of AT2 receptor does not markedly impact the stability of renin-angiotensin system and the inductive function of AT2 receptor is compensated in a way remaining to be clarified.

Pharyngeal airway changes associated with mandibular advancement.

This study analyzes changes in the anteroposterior dimension of the oropharynx as determined from lateral cephalometric radiographs on 26 patients who have undergone mandibular advancement. Increases in the sagittal dimensions of the oropharynx were unpredictable and tended to decrease with time, suggesting that mandibular advancement may be an unreliable method of treating obstructive sleep apnea. The most stable long-term results were found in those cases with narrowing of the oropharynx preoperatively.

[Tumor necrosis factor alpha in IgA nephropathy].

Tumor necrosis factor alpha (TNF alpha) in serum and supernate of peripheral blood lymphocyte stimulated by PHA in 100 cases of IgA nephropathy (IgAN) was evaluated by means of ELISA with TNF alpha monoclone antibody (T5 & E6). The results show that TNF alpha content in serum and supernatant was significantly higher in IgAN than in control (P < 0.01), and was increased markedly in IgAN with sclerosis (P < 0.01). It suggests that TNF alpha play an important role in cellular immunity of IgA nephropathy.

[Effect of serum from IgA nephropathy patients on IL-1 production from P388 D1 cell lines].

The study was designed to investigate IL-1 production from P388D1 cell using serum from 40 cases with IgA nephropathy (IgAN) as stimulative factor. It was found that there was a relationship between IL-1 and renal morphological change. The result indicated that IL-1 production by P388D1 cell was much higher in the presence of the serum than that in the absence (CPM: 47597 +/- 26213 vs 36567 +/- 14377 P less than 0.05). The level of IL-1 correlated obviously to the renal morphologic changes (r = 0.406, P less than 0.05). It is suggested that in the serum of IgAN patients there are certain factors stimulating P388D1 cell to produce IL-1, which may contribute to the pathogenesis of IgAN.

[Monoclonal antibody against laminin a and b chains: preparation and its clinical application].

In present study, we developed a hybridoma cell line which secretes monoclonal antibody against Laminin (Mo-611). The MoAb produced was identified to be isotype of IgG1. It reacted with Laminin obtained from murine EHS sarcoma, the intensity of reaction declined in accompany with increment of dilution, and could be absorbed by Laminin in 1 u/ml. On western blotting, it bounded to Laminin A chain 400 KD and Laminin B chain 200 KD. On IF study of renal tissue, positive staining with Mo-611 could be detected in fetal GBM and TBM, normal adult glomerular mesangial area and cytoplasm of tubular epithelium. In case of IgA nephropathy, the amount of deposits in mesangial area increased while in membranous nephropathy deposits along the capillary loop was also abundant in amount. In conclusion, the clinical application of McAb against Laminin might be helpful in the immunopathological diagnosis of glomerular diseases.

[A new monoclonal antibody against human tubular brush border: preparation and its application in membranous nephropathy].

A new monoclonal antibody (McAb) against human tubular brush border was successfully prepared by authors using the hybridoma technique. The McAb produced was identified to be isotype of IgG1 by IF and SDS-PAGE assay. It was unique for its purity and specificity. To demonstrate the clinical usefulness, the McAb was applied for immunopathological study in 94 cases of renal biopsy of glomerular diseases. This McAb was distinguished by its specific deposition along the human tubular brush border and the subepithelial region in certain type of glomerular disease, particularly the MGN. Identification of this McAb might contribute to the immunopathological diagnosis of GN.