A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review

BackgroundGlutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few case reports and research on anti-GAD65 antibody-associated encephalitis in adults, such cases are extremely rare in pediatric cases.MethodsFor the first time, we report a case of anti-GAD65-positive autoimmune encephalitis associated with autoimmune polyendocrine syndrome (APS) type II. We reviewed previously published pediatric cases of anti-GAD65 autoimmune encephalitis to discuss their clinical features, laboratory tests, imaging findings, EEG patterns, and prognosis.Case presentationAn 8-year-old, male child presented to the outpatient department after experiencing generalized convulsions for twenty days. The child was admitted for epilepsy and had received oral sodium valproate (500 mg/day) in another center, where investigations such as USG abdomen and MRI brain revealed no abnormalities, however, had abnormal EEG with diffuse mixed activity in the left anterior middle prefrontal temporal region. On the follow-up day, a repeat blood test showed a very low serum drug concentration of sodium valproate hence the dose was increased to 750 mg/day. Then, the child experienced adverse effects including increased sleep, thirst, and poor appetite, prompting the parents to discontinue the medication. A repeat MRI showed increased signals on FLAIR sequences in the right hippocampus hence admitted for further management. The child's past history included a diagnosis of hypothyroidism at the age of 4, and receiving levothyroxine 75 mcg once daily. His parents are healthy with no history of any similar neurological, autoimmune, or genetic diseases, but his uncle had a history of epilepsy. At presentation, he had uncontrolled blood glucose levels with elevated HbA1c levels. Additionally, the serum and CSF autoantibodies were positive against the anti-GAD65 antibody with the titer of 1:100 and 1:32 respectively. The patient was managed with a mixed type of insulin regimen and received first-line immunotherapy (intravenous immunoglobulin, IVIG) for five consecutive days, followed by oral prednisone and sodium valproate as an antiepileptic drug. Upon achieving a favorable clinical outcome, the patient was discharged with oral medications.ResultsAmong the 15 pediatric patients reported in this literature, nine presented with limbic encephalitis (LE), three with extralimbic encephalitis (ELE), and three with a combination of limbic and extralimbic encephalitis. Most of these cases exhibited T2-W FLAIR hyperintensities primarily localized to the temporal lobes in the early phase, progressing to hippocampal sclerosis/atrophy in the later phase on MRI. EEG commonly showed slow or spike waves on frontotemporal lobes with epileptic discharges. Prognostic factors varied among patients, with some experiencing persistent refractory seizures, type-1 diabetes mellitus (T1DM), persistent memory impairment, persistent disability requiring full assistance, and, in severe cases, death.ConclusionOur findings suggest that anti-GAD65 antibody-positive autoimmune encephalitis patients may concurrently present with other APS. Our unique case presented with multiple endocrine syndromes and represents the first reported occurrence in children. Early diagnosis and timely initiation of immunotherapy are crucial for improving clinical symptoms and reducing the likelihood of relapses or permanent disabilities. Therefore, emphasis should be placed on prompt diagnosis and appropriate treatment implementation to achieve better patient outcomes

QSYQ Attenuates Oxidative Stress and Apoptosis Induced Heart Remodeling Rats through Different Subtypes of NADPH-Oxidase

We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure (HF) in clinical practice in China, on a rat heart failure (HF) model. 3 groups were divided: HF model group (LAD ligation), QSYQ group (LAD ligation and treated with QSYQ), and sham-operated group. After 4 weeks, rats were sacrificed for cardiac injury measurements. Rats with HF showed obvious histological changes including necrosis and inflammation foci, elevated ventricular remodeling markers levels(matrix metalloproteinases-2, MMP-2), deregulated ejection fraction (EF) value, increased formation of oxidative stress (Malondialdehyde, MDA), and up-regulated levels of apoptotic cells (caspase-3, p53 and tunnel) in myocardial tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting those events. The improvement of QSYQ was accompanied with a restoration of NADPH oxidase 4 (NOX4) and NADPH oxidase 2 (NOX2) pathways in different patterns. Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs pathway seemed to be the critical potential targets for QSYQ to reduce the remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and Caspase3, thus to reduce the hypertrophy and apoptosis, and eventually provide a synergetic cardiac protective effect

Drugs and herbs given to prevent hepatotoxicity of tuberculosis therapy: systematic review of ingredients and evaluation studies

Background: Drugs to protect the liver are frequently prescribed in some countries as part of treatment for tuberculosis. The biological rationale is not clear, they are expensive and may do harm. We conducted a systematic review to a) describe the ingredients of "liver protection drugs"; and b) compare the evidence base for the policy against international standards. Methods: We searched international medical databases (MEDLINE, EMBASE, LILACS, CINAHL, Cochrane Central Register of Controlled Trials, and the specialised register of the Cochrane Infectious Diseases Group) and Chinese language databases (CNKI, VIP and WanFang) to April 2007. Our inclusion criteria were research papers that reported evaluating any liver protection drug or drugs for preventing liver damage in people taking anti-tuberculosis treatment. Two authors independently categorised and extracted data, and appraised the stated methods of evaluating their effectiveness. Results: Eighty five research articles met our inclusion criteria, carried out in China (77), India (2), Russia (4), Ukraine (2). These articles evaluated 30 distinct types of liver protection compounds categorised as herbal preparations, manufactured herbal products, combinations of vitamins and other non-herbal substances and manufactured pharmaceutical preparations. Critical appraisal of these articles showed that all were small, poorly conducted studies, measuring intermediate outcomes. Four trials that were described as randomised controlled trials were small, had short follow up, and did not meet international standards. Conclusion: There is no reliable evidence to support prescription of drugs or herbs to prevent liver damage in people on tuberculosis treatment

Enhance the Transfer Capacity of Multiplex Networks

Most complex real systems are found to have multiple layers of connectivity and required to be modelled as multiplex networks. One of the extremely critical problems is to reduce the congestion and enhance the transfer capacity, especially in real communication networks with a big data environment. A novel and effective strategy to improve traffic and control congestion is proposed by adding edges according to their weights which are defined by the topology structural properties. Furthermore, which layer is more effective when our strategy is applied is discussed based on its topology structure. Adding edges between nodes whose product of multiplex network betweenness is the highest is confirmed to be more effective, particularly in the layer with stronger community structure. Simulation experiments on both computer-generated and real-world networks demonstrate that our strategy can enhance the transfer capacity of multiplex networks significantly, which is in good agreement with our analysis

Grey Relational Grade Based Quantitative Analysis of the Factors Influencing the Load Characteristics of A Power Grid

Regarding analysis of load characteristics of a power grid, there are multiple factors that influence the variation of load characteristics. Among these factors, the influence of different ones on the change of load characteristic is somewhat different, thus the degree of influence of various factors needs to be quantified to distinguish the main and minor factors of load characteristics. Based on this, the grey relational analysis in the grey system theory is employed as the basis of mathematical model in this paper. Firstly, the main factors affecting the load characteristics of a power grid are analysed. Then, the principle of quantitative analysis of the influencing factors by using grey relational grade is introduced. Lastly, the load of Guangzhou power grid is selected as the research object, thereby the main factor of temperature affecting the load characteristics is quantitatively analysed, such that the correlation between temperature and load is established. In this paper, by investigating the influencing factors and the degree of influence of load characteristics, the law of load characteristics changes can be effectively revealed, which is of great significance for power system planning and dispatching operation

Grey Relational Grade Based Quantitative Analysis of the Factors Influencing the Load Characteristics of A Power Grid

Regarding analysis of load characteristics of a power grid, there are multiple factors that influence the variation of load characteristics. Among these factors, the influence of different ones on the change of load characteristic is somewhat different, thus the degree of influence of various factors needs to be quantified to distinguish the main and minor factors of load characteristics. Based on this, the grey relational analysis in the grey system theory is employed as the basis of mathematical model in this paper. Firstly, the main factors affecting the load characteristics of a power grid are analysed. Then, the principle of quantitative analysis of the influencing factors by using grey relational grade is introduced. Lastly, the load of Guangzhou power grid is selected as the research object, thereby the main factor of temperature affecting the load characteristics is quantitatively analysed, such that the correlation between temperature and load is established. In this paper, by investigating the influencing factors and the degree of influence of load characteristics, the law of load characteristics changes can be effectively revealed, which is of great significance for power system planning and dispatching operation

Genome-wide transcriptomic analysis of the response of Botrytis cinerea to wuyiencin.

Grey mould is caused by the ascomycetes Botrytis cinerea in a range of crop hosts. As a biological control agent, the nucleoside antibiotic wuyiencin has been industrially produced and widely used as an effective fungicide. To elucidate the effects of wuyiencin on the transcriptional regulation in B. cinerea, we, for the first time, report a genome-wide transcriptomic analysis of B. cinerea treated with wuyiencin. 2067 genes were differentially expressed, of them, 886 and 1181 genes were significantly upregulated and downregulated, respectively. Functional categorization indicated that transcript levels of genes involved in amino acid metabolism and those encoding putative secreted proteins were altered in response to wuyiencin treatment. Moreover, the expression of genes involved in protein synthesis and energy metabolism (oxidative phosphorylation) and of those encoding ATP-binding cassette transporters was markedly upregulated, whereas that of genes participating in DNA replication, cell cycle, and stress response was downregulated. Furthermore, wuyiencin resulted in mycelial malformation and negatively influenced cell growth rate and conidial yield in B. cinerea. Our results suggest that this nucleoside antibiotic regulates all aspects of cell growth and differentiation in B. cinerea. To summarize, some new candidate pathways and target genes that may related to the protective and antagonistic mechanisms in B. cinerea were identified underlying the action of biological control agents

Collaborative Routing Protocol Based on Hydrodynamics for Wireless Sensor Networks

Collaborative routing protocol design is hard work for wireless sensor networks (WSNs), especially for the large scale WSNs. The complexity and collaboration associated with the routing protocol design must be taken into account. A collaborative hydrodynamics routing (HR) protocol based on hydrodynamic theory is proposed in this paper, which aims at prolonging the network lifetime and adapting to the variety of network scales. Packets for forwarding in sensor networks can be analogous to fluid elements moving in a fluid field. Sink nodes are similar to the sink flows and source nodes are similar to the source flows; and packets would flow from sources to sinks under potential flow. Simulation results show that our approach has a great advantage as it offers a significant improvement in the aspects of decreasing complexity and prolonging network lifetime and demonstrates high performance for the improvement in collaboration of routing protocol. Comparing with conventional AODV protocol, HR achieves higher successful delivery rate and longer network lifetime by 50% and 40%, respectively