Development and global validation of a 1-week-old piglet head finite element model for impact simulations.

PURPOSE: Child head injury under impact scenarios (e.g. falls, vehicle crashes, etc.) is an important topic in the field of injury biomechanics. The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties. However, up to date, piglet head models with accurate geometry and material properties, which have been validated by impact experiments, are seldom. We aim to develop such a model for future research. METHODS: In this study, first, the detailed anatomical structures of the piglet head, including the skull, suture, brain, pia mater, dura mater, cerebrospinal fluid, scalp and soft tissue, were constructed based on CT scans. Then, a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models. Finally, the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model. RESULTS: Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature. The average peak force and duration of the guide drop tower test were similar to that of the simulation, with an error below 10%. The inaccuracy was below 20%. The average peak force and duration reported in the literature were comparable to those of the simulation, with the exception of the duration for an impact energy of 11 J. The results showed that the model was capable to capture the response of the pig head. CONCLUSION: This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.

Late-onset Leigh syndrome without delayed development in China: A case report.

BACKGROUND: Leigh syndrome (LS) is one of the most common mitochondrial diseases in infants and children. LS often manifests as early-onset with delayed phenotypic development. However, late-onset LS with normal development and white matter lesions in the brain is rarely reported, thereby highlighting the phenotypic variability of LS expression. CASE SUMMARY: We report a 12-year-old boy who presented with an unusual late-onset and fulminant form of LS that is maternally inherited without developmental delay. The patient was admitted to the hospital with symptoms of ptosis and somnolence, and died within 2 mo. Analysis of peripheral blood leukocytes showed a homoplasmic m.9176T>C mutation in the patient. Magnetic resonance imaging also revealed lesions in bilateral white matter as well as symmetrical lesions in the basal ganglia and brain stem. The patient was diagnosed with LS. The patient was treated with vitamin C, vitamin D, and adenosine-triphosphate. The patient died within 2 mo of hospital admission. CONCLUSION: LS can present in both infants and older children with different phenotypes.

Case Report: m.13513 G>A Mutation in a Chinese Patient With Both Leigh Syndrome and Wolff-Parkinson-White Syndrome.

A number of causative mutations in mitochondrial and nuclear DNA have been identified for Leigh syndrome, a neurodegenerative encephalopathy, including m. 8993 T>G, m.8993 T>C, and m.3243A>G mutations in the MTATP6, MTATP6, and MT-TL1 genes, respectively, which have been reported in Leigh syndrome patients in China. The m.13513 G>A mutation has been described only a few times in the literature and not previously reported in China. Here we report the case of a 15-month-old boy who presented with ptosis and developmental delay and was diagnosed with Leigh syndrome and well as Wolff-Parkinson-White (WPW) syndrome. The m.13513 G>A mutation was found in DNA from blood. He was intubated due to respiratory failure and died at 23 months of age. The m.13513 G>A mutation in the ND5 gene of mitochondrial DNA is associated with Leigh syndrome and WPW syndrome; however, this is the first report of this mutation in a patient in China, highlighting the geographical and racial variability of Leigh syndrome.

Posterior reversible encephalopathy syndrome induced by food poisoning in a pediatric patient: a case report.

Posterior reversible encephalopathy syndrome (PRES) can develop in patients following exposure to multiple triggers, including blood pressure fluctuations, kidney diseases, immunosuppressive agents, chemotherapy, or autoimmune disorders. However, to the best of our knowledge, the development of PRES secondary to food poisoning has not been previously reported, especially in a pediatric patient. Here, we report a 13-year-old boy who presented with PRES following the consumption of palmatum (a chicken feet dish). The patient presented with headache, vomiting, and altered consciousness. Neuroimaging findings revealed white matter hyperintensities in a bilateral, symmetrical, and parieto-occipital pattern. The patient was diagnosed with PRES and was managed with fluid expansion and a short-term mannitol regimen (1 g/kg every 12 hours for 3 days). Neuroimaging findings returned to normal at 8 days after admission. Food poisoning may therefore be a new possible trigger for PRES. A timely PRES diagnosis is recommended to prevent possible central nervous system complications.

Dynamic Expression of CX36 Protein in Kainic Acid Kindling induced Epilepsy.

Connexin (Cx) 36 is known to be a component of gap junctions, and has been suggested to play an important role in epilepsy. In order to determine dynamic changes of Cx36 protein expression in epilepsy and investigate the role of Cx36 in electroencephalographic activity and pathogenesis, we utilized kainic acid (KA) to induce epileptogenesis. We found that epileptic discharges began 71.8 ± 23.7 s after KA administration. Spike frequency and amplitude of epileptiform activity reached maximal levels at 30 ± 5.2 min. The maximum level of spike frequency and amplitude of epileptiform activity was 13.9 ± 0.3 Hz and 198 ± 14.3mV respectively. Employing Western blotting and immunohistochemistry, we demonstrated that hippocampal Cx36 protein expression was significantly increased 6 h after KA kindling compared to control or sham groups, but decreased in 3 d and 7d groups. Our results suggested that the dynamic change of Cx36 expression may play an important role inepilepsy, and the specific manipulation of Cx36 expression may be a potential target for the treatment of epilepsy.

Activation of Sonic hedgehog signal by Purmorphamine, in a mouse model of Parkinson's disease, protects dopaminergic neurons and attenuates inflammatory response by mediating PI3K/AKt signaling pathway.

In Parkinson's disease (PD), microglial activation-mediated neuroinflammation is associated with dopaminergic neurons degeneration in the substantia nigra pars compacta. Previous studies that have investigated this neurodegenerative disease have reported that the Sonic hedgehog (SHH) signaling pathway, through inhibiting the inflammatory processes, exerts a beneficial neuroprotective effect. However, the mechanisms underlying the anti­inflammatory and neuroprotective effects of this signaling pathway remain poorly understood. The present study aimed to further investigate these mechanisms in vitro and in vivo. At first, BV2 microglial cells treated with lipopolysaccharide (LPS) were used to induce an inflammatory response. It was observed that the activation of SHH signaling by Purmorphamine attenuated the LPS­induced inflammatory response, increased the expression of transforming growth factor­ß1 through the phosphatidylinositol 3­kinase (PI3K)/AKT serine/threonine kinase (Akt) intracellular signaling pathway and inhibited nuclear receptor subfamily 4 group A member 2, independently of the PI3K/Akt signaling pathway. Furthermore, the blockade of the PI3K/Akt signaling pathway by intranasal administration of LY294002, significantly reduced the SHH­associated neuroprotective effects on dopaminergic neurons, improved motor functions, and increased the microglial activation and inflammatory response in a mouse model of PD induced using 1­methyl­4­phenyl­1,2,3,6­tetrahydropyridine. In conclusion, the data of the present study reported that anti­inflammatory and neuroprotective effects can be obtained in BV2 microglial cells and in a mouse model of PD by successive activation of the SHH and PI3K/Akt signaling pathways.

Effect of connexin 36 blockers on the neuronal cytoskeleton and synaptic plasticity in kainic acid-kindled rats.

In this study we investigated the potential anti-epileptogenic effect of neuronal connexin Cx36 gap junction blockage via inhibition of microtubule-associated protein 2 (MAP-2) and synaptophysin (SYP) overexpression. Thirty adult male Wistar rats were divided into five groups (six animals per group): control, sham, carbenoxolone (CBX), quinine (QN), and quinidine (QND). An epilepsy model was produced by injecting kainic acid (KA) into the rat amygdala. Broad-spectrum and selective blockers of the Cx36 channel (CBX, QN, and QND) were administered via intraperitoneal injection. Expression of MAP-2 and SYP was assessed by immunofluorescent and immunohistochemical examination. Expression of MAP-2 and SYP was significantly increased after KA administration in the sham group compared with the control group. Expression of MAP-2 and SYP was significantly decreased in the CBX, QN, and QND groups compared with the sham group. The results provide new evidence regarding the key role of MAP-2 and SYP overexpression in three important mechanisms: the modulation of neuronal plasticity, hyperexcitability of the hippocampal neuronal network, and persistent seizure discharge. Furthermore, the reversal of MAP-2 and SYP overexpression following administration of Cx36 channel blockers indicates a potential role for Cx36 channel blockers in anti-epileptogenic treatment and in doing so, highlights a critical need for further investigation of these compounds.

Ethyl 4-acetamido-3-acet-oxy-2-benzyl-3-methyl-butano-ate.

The crystal structure of the title compound, C(18)H(25)NO(5), is stabilized by inter-molecular N-H⋯O hydrogen bonds, which form inversion dimers. The ethyl group is disordered over two positions in a 0.651 (12):0.349 (12) ratio.

Ethyl 1-(4-chloro-benz-yl)-3-(4-fluoro-phen-yl)-1H-pyrazole-5-carboxyl-ate.

In the title compound, C(19)H(16)ClFN(2)O(2), the pyrazole ring makes dihedral angles of 5.15 (6) and 77.72 (6)°, with the fluoro-phenyl and chloro-phenyl rings, respectively.

[Investigation on the molecular mechanisms of anti-hepatocarcinoma herbs of traditional Chinese medicine by cell cycle microarray].

OBJECTIVE: To design DNA microarray and investigate the molecular anti-tumor mechanism of herbs of traditional Chinese medicine. METHOD: cDNA microarrays consisting of 56 probes representing 24 human cell cycle genes were constructed, Four anti-hepatocarcinoma herbs including Radix Linderae, Hebra Artemisiae Annuae, Radix Amebiae, Radix Astragli, were chosen. Effects of herbs on SMMC-7721 cell cycle were observed by flow cytometry assay. Effects of herbs on cell cycle gene expression in SMMC-7721 cells were analyzed by comparing hybridization of Dig-Labeled cDNAs from herb-treated cells and cDNAs from untreated cells. RESULT: Expressions of cell cycle geneswere changed in different degrees after herbs treated. Some genes were down-regulated and some genes were up-regulated. The changes in gene expression agreed with the results of flow cytometry assay. CONCLUSION: The results suggest that these herbs may have effects on cell cycle and DNA damage checkpoint genes which may be the mechanism of the herbs, and DNA microarray can be used to investigate the biological function of extracts of traditional Chinese medicine.

[Detection of differentially expressed genes in hepatocellularcarcinoma cells SMMC-7721 treated with Typhonium giganteum extract by mRNA differential display].

OBJECTIVE: To screen and identify the differentially expressed genes in hepatocellular carcinoma cells SMMC-7721 responsing to the aqueous extract from dried powdered rhizomes of Typhonium giganteum (AEoTGE). METHOD: The response of hepatocellular carcinoma cells SMMC-7721 to AEoTGE was explored with the technique of mRNA differential display. RESULT: After hepatocarcinoma cells SMMC-7721 were treated by AEoTGE for 36 hours, 1 gene expression was upgrade and 1 gene expression was downgrade induced by AEoTGE. CONCLUSION: The research has provided important clues for the molecular mechanism of how hepatocarcinoma cells responseing to T. giganteum.