Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to ...control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism.
Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D
(VD
).
A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD
, other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316).
Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.
Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by transient mild symptoms of encephalopathy and a reversible ...lesion in the splenium of the corpus callosum on magnetic resonance imaging (MRI). It is often triggered by infection. The common pathogens of MERS are viruses, especially influenza virus. However, Mycoplasma pneumoniae (M.pneumoniae) are relatively rare pathogens for MERS.
Here we report two paediatric cases of M.pneumoniae infection-induced MERS. The diagnosis of M.pneumoniae infection was established based on polymerase chain reaction (PCR) and specific serum antibodies (IgM). Both of the two patients presented with mild encephalopathy manifestations and recovered completely within a few days. The initial MRI showed a lesion in the central portion of the splenium of the corpus callosum, which completely resolved on the seventh and eighth day after admission for case 1 and case 2. Lumbar puncture was performed in both patients, which revealed no pleocytosis. In case 1, the patient had hyponatremia, peripheral facial nerve paralysis, and rash. To the best of our knowledge, it is the first MERS case associated with peripheral nerve damage. In case 2, interleukin-6(IL-6) was moderately increased in the cerebrospinal fluid (CSF). It suggested that IL-6 may play a role in the pathogenesis of M.pneumoniae-induced MERS.
Our study enriches the available information on the pathogens of MERS and provides valuable data for better understanding of this syndrome.
Selectively targeting leukemia stem cells (LSCs) is a promising approach in treating acute myeloid leukemia (AML), for which identification of such therapeutic targets is critical. Increasing lines ...of evidence indicate that FBXO22 plays a critical role in solid tumor development and therapy response. However, its potential roles in leukemogenesis remain largely unknown.
We established a mixed lineage leukemia (MLL)-AF9-induced AML model with hematopoietic cell-specific FBXO22 knockout mice to elucidate the role of FBXO22 in AML progression and LSCs regulation, including self-renewal, cell cycle, apoptosis and survival analysis. Immunoprecipitation combined with liquid chromatography-tandem mass spectrometry analysis, Western blotting and rescue experiments were performed to study the mechanisms underlying the oncogenic role of FBXO22.
FBXO22 was highly expressed in AML, especially in MLL-rearranged (MLLr) AML. Upon FBXO22 knockdown, human MLLr leukemia cells presented markedly increased apoptosis. Although conditional deletion of Fbxo22 in hematopoietic cells did not significantly affect the function of hematopoietic stem cells, MLL-AF9-induced leukemogenesis was dramatically abrogated upon Fbxo22 deletion, together with remarkably reduced LSCs after serial transplantations. Mechanistically, FBXO22 promoted degradation of BACH1 in MLLr AML cells, and overexpression of BACH1 suppressed MLLr AML progression. In line with this, heterozygous deletion of BACH1 significantly reversed delayed leukemogenesis in Fbxo22-deficient mice.
FBXO22 promotes MLLr AML progression by targeting BACH1 and targeting FBXO22 might be an ideal strategy to eradicate LSCs without influencing normal hematopoiesis.
β-Amyloid protein (Aβ) is thought to cause neuronal loss in Alzheimer's disease (AD). Aβ treatment promotes the re-activation of a mitotic cycle and induces rapid apoptotic death of neurons. However, ...the signaling pathways mediating cell-cycle activation during neuron apoptosis have not been determined. We find that Wnt5a acts as a mediator of cortical neuron survival, and Aβ
promotes cortical neuron apoptosis by downregulating the expression of Wnt5a. Cell-cycle activation is mediated by the reduced inhibitory effect of Wnt5a in Aβ
treated cortical neurons. Furthermore, Wnt5a signals through the non-canonical Wnt/Ca
pathway to suppress cyclin D1 expression and negatively regulate neuronal cell-cycle activation in a cell-autonomous manner. Together, aberrant downregulation of Wnt5a signaling is a crucial step during Aβ
induced cortical neuron apoptosis and might contribute to AD-related neurodegeneration.
Abstract Background Reversible bilateral striatal necrosis associated with Mycoplasma pneumoniae (M. pneumoniae) infection is a rare neurological disease. The exact pathogenic mechanism remains ...unknown. Patient We report reversible bilateral striatal lesions with a favorable outcome secondary to M. pneumoniae infection in an 8-year-old Chinese girl. Cranial MRI showed abnormal signals in bilateral striatum, which disappeared 8 months later. To better understand the pathogenesis of this encephalopathy, we examined cytokines levels in serum and cerebrospinal fluid from this patient. The results revealed the concentrations of interleukin-6 and interleukin-8 increased significantly in serum (26 pg/mL and 66 pg/mL, respectively) and cerebrospinal fluid (122 pg/mL and 325 pg/mL, respectively), and were reduced markedly after the therapy. Intrathecal production of interleukin-6 and interleukin-8 is probably related to the pathogenesis of striatal lesions caused by M. pneumoniae . These cytokines may cause local vascular injury, and finally leading to local vascular occlusion. Conclusion Our results suggest that interleukin-6 and interleukin-8 may play important roles in the pathogenesis of this disease. This is the first report to describe the role of cytokines in this condition and relevant literature is reviewed. Our findings may lead to better understanding of the pathogenesis of M. pneumoniae -associated striatal lesions.
Guillain-Barré syndrome is the most common acute peripheral neuropathy in children in most countries. The cause and pathogenesis of the disease have yet to be clarified. There have been only a few ...reports of Guillain-Barré syndrome resulting from parasite infections worldwide, no cases of Guillain-Barré syndrome after lung fluke infection have been reported. We report a case of an 8-year-old male patient with Guillain-Barré syndrome after lung fluke infection. The child had a history of consumption of undercooked crabs. He was diagnosed with paragonimiasis. The patient experienced paralysis of and pain in the lower limbs about 3 weeks after symptom onset. Neurologic and electrophysiologic examination findings supported the diagnosis of Guillain-Barré syndrome. Parasitic infections should also be considered when determining which antecedent infection is associated with Guillain-Barré syndrome.
Background
Wilson’s disease (WD) is an autosomal recessive genetic disorder of copper metabolism, caused by mutations in the
ATP7B
gene, resulting in copper accumulation in the liver, brain, kidney, ...and cornea and leading to significant disability or death if untreated. Early diagnosis and proper therapy usually predict a good prognosis, especially in pre-symptomatic WD. Genetic testing is the most accurate and effective diagnostic method for early diagnosis.
Methods
The clinical and biochemical features of three unrelated Han Chinese families with pre-symptomatic WD were reported. The molecular defects in these families were investigated by polymerase chain reaction and DNA sequencing. Hundred healthy children with the same ethnic background served as controls. Bioinformatic tools (polymorphism phenotyping-2, sorting intolerant from tolerant, protein analysis through evolutionary relationships, and predictor of human deleterious single nucleotide polymorphisms) were combined and used to predict the functional effects of mutations.
Results
We identified 2 novel
ATP7B
mutations (p.Leu692Pro and p.Asn728Ser) and 3 known mutations (p.Met769fs, p.Arg778Leu and p.Val1216Met) in these Chinese WD families. These mutations were not observed in the 100 normal controls. The bioinformatic method showed that p.Leu692Pro and p.Asn728Ser mutations are pathogenic.
Conclusions
Our research enriches the mutation spectrum of the
ATP7B
gene worldwide and provides valuable information for studying the mutation types and mode of inheritance of
ATP7B
in the Chinese population. Liver function analysis and genetic testing in young children with WD are necessary to shorten the time to the initiation of therapy, reduce damage to the liver and brain, and improve prognosis.
The crude polysaccharide was obtained from
Gynostemma pentaphyllum Makino by water extraction followed by ethanol precipitation. The polysaccharide was successively purified by chromatography on ...DEAE-52 and SephadexG-150 column, and three polysaccharide fractions were obtained and termed GPP1-a, GPP2-b, and GPP3-a, respectively. The administration with GPP1-a markedly prolonged exhaustive exercise time of the mice. Structural features of GPP1-a were investigated by a combination of instrumental and chemical analyses, including atomic force microscope (AFM), scanning electron microscope (SEM), partial acid hydrolysis, periodate oxidation, Smith degradation, methylation analysis, gas chromatography–mass spectrometry (GC–MS) analysis and NMR spectroscopy. The results indicate that GPP1-a has a backbone of (1
→
4)-linked α-
d-Glucose residues, which occasionally branches at O-6. The branches are mainly composed of (1
→
6)-linked α-
d-Glucose, (1
→
3)-linked β-
d-Galactose and (1
→
6)-linked α-
d-Galactose residues, and terminated with β-
d-Galactose residues and β-
l-Arabinose residues.
Aim: To explore the mechanism of topiramate‐induced weight loss in epilepsy children by monitoring metabolism indices.
Methods: Children with epilepsy were treated with topiramate at their first ...clinical visit. Metabolism indices including body mass index (BMI) and its SD scores, leptin, adiponectin, leptin/adiponectin (L/A), lipid profile‐insulin and Homeostasis Model Assessments (HOMA) index were collected before and after treatment.
Results: Topiramate treatment significantly reduced L/A (t = 2.156, p = 0.031), and markedly increased the serum level of adiponectin (t = 3.124, p = 0.002). Moreover, there were no relationships between the metabolism indices and dosages of topiramate (p > 0.05).
Conclusion: Our studies find that topiramate treatment in epilepsy children increases energy metabolism, resulting in weight loss. It has been demonstrated that adiponectin play a significant role in metabolic regulations.
To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT).
Children with a clinical diagnosis of early-onset CMT were selected for the study. ...Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed.
A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (
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