Publications by authors named "Qing-Xia Kong"

12 Publications

  • Page 1 of 1

Two siblings suffering from Angelman Syndrome with a novel c.1146T>G mutation in UBE3A: A case report.

Biomed Rep 2022 Jun 19;16(6):48. Epub 2022 Apr 19.

Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China.

Angelman syndrome (AS) is an autosomal dominant neurodevelopmental genetic disease with maternal imprint, which is associated with the presence of the abnormal chromosome 15q11-q13, and the loss of maternal specific expression of ubiquitin-protein ligase E3A (UBE3A). The expression levels of UBE3A depend on the parental origin and exhibit tissue specificity. In normal brain tissues, the maternal UBE3A gene is actively expressed, whereas the paternal UBE3A gene is not. In total, ~85% of pediatric patients with AS present with epilepsy within their 3rd year of life. This condition is usually difficult to control with medical treatment. An 8-year-old female visited the Affiliated Hospital of Jining Medical University due to frequent epilepsy. Her clinical manifestations included specific facial features, moderate mental retardation and frequent seizures. It was interesting to note that her 15-year-old sister exhibited similar clinical manifestations to those of AS. The results of the electroencephalogram and the imaging examinations were also in line with the characteristics of AS. In order to further clarify the diagnosis, all the suspected genes in her sister and in their parents were sequenced. The multiplex ligation-dependent probe amplification project of the Angel/chubby and copy number variation (CNV) sequencing were assessed concomitantly to identify the pathogenic genes responsible for the development of AS. The latter occurs due to the missense mutation c.1146T>G, which results in asparagine replacement by lysine at position 382 (p.Asn382Lys) in exon 7. This amino acid change affects the normal expression of UBE3A; the mutation is a novel mutation, which, to the best of our knowledge, has not been previously reported. Relevant large fragments of mutations and methylation abnormalities were not found in the associated genes. The data further revealed absence of 25-bp repeat mutations at the shear mutation site of exon 1 of the small nuclear ribonucleoprotein polypeptide N gene in the subjects examined. No suspected CNV was found following analysis.
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http://dx.doi.org/10.3892/br.2022.1531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112374PMC
June 2022

Spatiotemporal Expression of SphK1 and S1PR2 in the Hippocampus of Pilocarpine Rat Model and the Epileptic Foci of Temporal Lobe Epilepsy.

Front Cell Dev Biol 2020 8;8:800. Epub 2020 Oct 8.

Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, China.

Temporal lobe epilepsy (TLE) is a severe chronic neurological disease caused by abnormal discharge of neurons in the brain and seriously affect the long-term life quality of patients. Currently, new insights into the pathogenesis of TLE are urgently needed to provide more personalized and effective therapeutic strategies. Accumulating evidence suggests that sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate receptor 2 (S1PR2) signaling pathway plays a pivotal role in central nervous system (CNS) diseases. However, the precise altered expression of SphK1 and S1PR2 in TLE is remaining obscure. Here, we have confirmed the expression of SphK1 and S1PR2 in the pilocarpine-induced epileptic rat hippocampus and report for the first time the expression of SphK1 and S1PR2 in the temporal cortex of TLE patients. We found an increased expression of SphK1 in the brain from both epileptic rats and TLE patients. Conversely, S1PR2 expression level was markedly decreased. We further investigated the localization of SphK1 and S1PR2 in epileptic brains. Our study showed that both SphK1 and S1PR2 co-localized with activated astrocytes and neurons. Surprisingly, we observed different subcellular localization of SphK1 and S1PR2 in epileptic brain specimens. Taken together, our study suggests that the alteration of the SphK1/S1PR2 signaling axis is closely associated with the course of TLE and provides a new target for the treatment of TLE.
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http://dx.doi.org/10.3389/fcell.2020.00800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578367PMC
October 2020

Brain Proteomic Profiling in Intractable Epilepsy Caused by TSC1 Truncating Mutations: A Small Sample Study.

Front Neurol 2020 29;11:475. Epub 2020 May 29.

Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, China.

Tuberous sclerosis complex (TSC) is a genetic disease characterized by seizures, mental deficiency, and abnormalities of the skin, brain, kidney, heart, and lungs. TSC is inherited in an autosomal dominant manner and is caused by variations in either the TSC1 or TSC2 gene. TSC-related epilepsy (TRE) is the most prevalent and challenging clinical feature of TSC, and more than half of the patients have refractory epilepsy. In clinical practice, we found several patients of intractable epilepsy caused by TSC1 truncating mutations. To study the changes of protein expression in the brain, three cases of diseased brain tissue with TSC1 truncating mutation resected in intractable epilepsy operations and three cases of control brain tissue resected in craniocerebral trauma operations were collected to perform protein spectrum detection, and then the data-independent acquisition (DIA) workflow was used to analyze differentially expressed proteins. As a result, there were 55 up- and 55 down-regulated proteins found in the damaged brain tissue with TSC1 mutation compared to the control. Further bioinformatics analysis revealed that the differentially expressed proteins were mainly concentrated in the synaptic membrane between the patients with TSC and the control. Additionally, TSC1 truncating mutations may affect the pathway of amino acid metabolism. Our study provides a new idea to explore the brain damage mechanism caused by TSC1 mutations.
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http://dx.doi.org/10.3389/fneur.2020.00475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326032PMC
May 2020

Compound heterozygous mutations in the gene cause Sjögren-Larsson syndrome: a case report.

Int J Neurosci 2020 Nov 29;130(11):1156-1160. Epub 2020 Jan 29.

Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272000, China.

Sjögren-Larsson syndrome is a rare, autosomal, recessive neurocutaneous disorder caused by mutations in the gene, which encodes the fatty aldehyde dehydrogenase enzyme. Deficiency in fatty aldehyde dehydrogenase results in an abnormal accumulation of toxic fatty aldehydes in the brain and skin, which cause spasticity, intellectual disability, ichthyosis, and other clinical manifestations. We present the clinical features and mutation analyses of a case of SLS. The family history and clinical data of the patient were collected. Genomic DNA was extracted from peripheral blood samples of the patient and her parents, and next-generation sequencing was performed. The candidate mutation sites that required further validation were then sequenced by Sanger sequencing. Bioinformatics software PSIPRED and RaptorX were used to predict the secondary and tertiary structures of proteins. The patient, a five-year-old girl with complaints of cough for three days and intermittent convulsions for seven hours, was admitted to the hospital. Other clinical manifestations included spastic paraplegia, mental retardation, tooth defects, and ichthyosis. Brain magnetic resonance imaging showed periventricular leukomalacia. Genetic screening revealed compound heterozygous mutations in the ALDH3A2 gene: a frameshift mutation c.779delA (p.K260Rfs*6) and a missense mutation c.1157A > G (p.N386S). Neither of the ALDH3A2 alleles in the compound heterozygote patient were able to generate normal fatty aldehyde dehydrogenase, which were likely responsible for her phenotype of Sjögren-Larsson syndrome. The compound heterozygous mutations found in the gene support the diagnosis of Sjögren-Larsson syndrome in the patient and expand the genotype spectrum of the gene.
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http://dx.doi.org/10.1080/00207454.2020.1716750DOI Listing
November 2020

[Altered expressions of SphK1 and S1PR2 in hippocampus of epileptic rats].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2019 Jul;35(4):308-311

Department of Neurology, Affiliated Hospital of Jining Medical University, Jining 272000.

Objective: To observe the expressions of sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate receptor 2 (S1PR2) in hippocampus of epileptic rats and to investigate the pathogenesis of SphK1 and S1PR2 in epilepsy.

Methods: One hundred and eight male Sprague-Dawley (SD) rats were randomly divided into control group (n=48) and pilocarpine (PILO) group (n=60). A robust convulsive status epilepticus (SE) was induced in PILO group rats by the application of pilocarpine. Control group rats were injected with respective of physiological saline. Pilocarpine group was randomly divided into 6 subgroups (n=8): acute group (E6 h, E1 d, E3 d), latent group (E7 d) and chronic group (E30 d, E56 d). Each subgroup has 8 control rats and 8 epileptic rats. Hippocampal tissue and brain slices were obtained from control rats and rats subjected to the Li-PILO model of epilepsy at 6 h, 1 d, 3 d,7 d,30 d and 56 d after status epilepticus (SE). Western blot technique was used to determine the expressions of SphK1 and S1PR2 in hippocampus at different point of time after pilocarpine treatment. Immunofluorescence was applied to detect the activation and proliferation of hippocampal astrocytes and the localization of SphK1 and S1PR2 in rat hippocampal astrocytes.

Results: Compared with control group, the levels of SphK1 in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d) were significantly increased while the expressions of S1PR2 were decreased in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d)(P<0.05 or P<0.01). Immunofluorescence results showed astrocyte activation and proliferation in hippocampus of epileptic (E7 d) rats (P<0.05). Confocal microscopy confirmed the preferential expressions of SphK1 and S1PR2 in epileptic rat(E7 d)hippocampal astrocytes.

Conclusion: The results indicate that SphK1 and S1PR2 may play an important role in the pathogenesis of epilepsy by regulating the activation and proliferation of hippocampal astrocytes and altering neuronal excitability.
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http://dx.doi.org/10.12047/j.cjap.5792.2019.065DOI Listing
July 2019

Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease.

Mol Med Rep 2019 Jun 5;19(6):4872-4880. Epub 2019 Apr 5.

Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China.

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by mutations in genes that encode subunits of the branched‑chain α‑ketoacid dehydrogenase (BCKD) complex. Impairment of the BCKD complex results in an abnormal accumulation of branched‑chain amino acids and their corresponding branched‑chain keto acids in the blood and cerebrospinal fluid, which are neurovirulent and may become life‑threatening. An 11‑day‑old boy was admitted to the hospital with paroxysmal spasticity of lower extremities. Of note, his 10‑year‑old sister presented similar symptoms during the neonatal period, and her condition was diagnosed as MSUD when she was 1.5 years old. Genetic screening was performed, and the boy and his sister exhibited two novel compound heterozygous mutations in the branched chain keto acid dehydrogenase E1 subunit β (BCKDHB) gene: A substitution from guanine to adenine in the coding region at position 1,076 (c.1,076G>A) in exon 10 and a deletion of a thymine at position 705 (c.705delT) in exon 6. The missense mutation c.1076G>A results in an amino acid substitution from arginine to lysine at position 359 (p.Arg359Lys), whereas the mutation c.705delT results in the replacement of a cysteine at position 235 with a stop codon (p.Cys235Ter). Neither of the BCKDHB alleles in the compound heterozygote patients is able to generate normal E1β subunits, resulting in a possible impairment of the activity of the BCKD complex. In the present study, it was hypothesized that the two novel heterozygous mutations in the BCKDHB gene found in the Chinese family may be responsible for the phenotype of the two siblings with MSUD.
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http://dx.doi.org/10.3892/mmr.2019.10133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522870PMC
June 2019

mutation causes the X-linked epilepsy-aphasia syndrome: A case report and review of literature.

World J Clin Cases 2018 Oct;6(12):570-576

Department of Neurology, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China.

The mutation in leads to a broad spectrum of phenotypic variability and manifests as an X-linked intellectual disability. However, we reported that the male patient in this study not only had intellectual disability but also epileptic seizures. In addition, there were progressive language impairment, attention deficit hyperactivity disorder and autism. Electroencephalograms showed continuous spike-and-wave during sleep. Genetic testing revealed a mutation of the gene (>, ) in the child that was not detected in the parents. Therefore, the child was diagnosed with X-linked epilepsy aphasia syndrome. Deletion of the gene has been rarely reported in epilepsy aphasia syndrome, but no mutation has been found in this gene. This report not only adds to the spectrum of epilepsy aphasia syndrome but also helps clinicians in diagnosis and genetic counseling.
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http://dx.doi.org/10.12998/wjcc.v6.i12.570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212609PMC
October 2018

Comparison of Elastic Properties of Bilateral Carotid Arteries in Relation to Site of Acute Ischemic Stroke Using Velocity Vector Imaging.

Chin Med J (Engl) 2015 Nov;128(21):2960-3

Shandong Provincial Key Laboratory of Diagnosis and Treatment of Cardio-Cerebral Vascular Diseases, Shandong Medical Imaging Research Institute, Shandong University, Jinan, Shandong 250021, China.

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http://dx.doi.org/10.4103/0366-6999.168075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756900PMC
November 2015

Increased plasmacytoid dendritic cells in Guillain-Barré syndrome.

J Neuroimmunol 2015 Jun 27;283:1-6. Epub 2015 Mar 27.

Departments of Medicine and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Guillain-Barré syndrome (GBS) is a post-infectious autoimmune disease. Dendritic cells (DCs) can recognize the pathogen and modulate the host immune response. Exploring the role of DCs in GBS will help our understanding of the disease development. In this study, we aimed to analyze plasmacytoid and conventional DCs in peripheral blood of patients with GBS at different stages of the disease: acute phase as well as early and late recovery phases. There was a significant increase of plasmacytoid DCs in the acute phase (p=0.03 vs healthy donors). There was a positive correlation between percentage of plasmacytoid DCs and the clinical severity of patients with GBS (r=0.61, p<0.001). Quantitative polymerase chain reaction and flow cytometry confirmed the aberrant plasmacytoid DCs in GBS. Thus, plasmacytoid DCs may participate in the development of GBS.
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http://dx.doi.org/10.1016/j.jneuroim.2015.03.019DOI Listing
June 2015

Suppressive oligodeoxynucleotides induced tolerogenic plasmacytoid dendritic cells and ameliorated the experimental autoimmune neuritis.

Immunol Lett 2015 Jul 5;166(1):13-8. Epub 2015 May 5.

Department of Neurology, Affiliated Hospital of Jining Medical College, Jining, Shandong Province, People's Republic of China. Electronic address:

Toll-like receptor (TLR) 9, recognizing different ligands, confers distinct features of plasmacytoid dendritic cells (pDCs). Our previous study demonstrated a role for TLR9 in the mechanism of experimental autoimmune neuritis (EAN). In this study, we explored whether suppressive oligodeoxynucleotides (sODN) could induce tolerogenic pDCs via TLR9 and thus promote the recovery of EAN. Effects of different TLR9 ligands, CpG ODN and sODN on P0 180-199 peptide-stimulated pDCs were measured by detecting the expression of co-stimulatory molecules, indoleamine 2,3-dioxygenase (IDO), secretion of Th1- and Th2-type cytokines and the TLR9 signaling pathway. CpG ODN- or sODN-treated pDCs were intravenously injected into the EAN mice and their effects were compared. Our data showed that P0180-199 peptides significantly promoted mRNA expression of co-stimulatory molecules (CD40, CD80 and CD86) in pDCs and induced secretion of Th1-type cytokines. Treatment of CpG ODN aggravated the effects of P0 180-199 peptides on pDCs; however, sODN had the opposite effects and significantly upregulated the IDO expression in pDCs. Further analysis showed that MYD88 is necessary for sODN to modulate the TLR9/NF-κB signaling in pDCs. Finally, the sODN-treated pDCs significantly promoted recovery of the EAN mice. Taken together, sODN could induce tolerogenic pDCs and thus ameliorate the EAN.
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http://dx.doi.org/10.1016/j.imlet.2015.04.007DOI Listing
July 2015

Study on the anti-cerebral ischemia effect of borneol and its mechanism.

Afr J Tradit Complement Altern Med 2014 2;11(1):161-4. Epub 2013 Nov 2.

Department of Neurology, Affiliated Hospital of Shan'dong Ji'ning Medical College, China; 272129.

Background: Borneol is the processed item from resin of Dryobalanops aromatica Gaertn. f. It can enhance the activity of antioxidant enzymes in brain tissue and reduce inflammatory response by improving the energy metabolism of ischemic brain regions, and thereby reduces brain tissue damage. The objective of this paper was to study the anti-cerebral ischemia effect of borneol and its mechanism.

Materials And Methods: The anti-cerebral ischemia effect of borneol was studied by ligation of bilateral common carotid arteries (CCA), and vagus nerves in mice and the acute cerebral ischemia-reperfusion experiment in rats.

Results: Compared with the blank and solvent control groups, the borneol low-; medium-; and high-dose groups can significantly prolong the gasping time of mice after decapitation, and extend the survival time of mice after ligation of bilateral CCA, and vagus nerves.

Conclusion: Compared with the Xueshuantong injection group, the prolongation of survival time of mice after ligation of bilateral CCA, and vagus nerves was more apparent in the high-dose borneol experimental group; each experimental group can significantly reduce the number of leukocyte infiltration, the number of ICAM-1-positive vessels, as well as the number of TNF-α-positive cells.

Conclusion: Borneol has an anti-cerebral ischemia effect.
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http://dx.doi.org/10.4314/ajtcam.v11i1.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957259PMC
November 2014

Silencing of miR155 promotes the production of inflammatory mediators in Guillain-Barré syndrome in vitro.

Inflammation 2013 Apr;36(2):337-45

Department of Neurology, Affiliated Hospital of Jining Medical College, 79 Guhuai Road, Jining, 272029, Shandong Province, People's Republic of China.

MicroRNA-155 (miR155) has been demonstrated as a central regulator of immune responses induced by inflammatory mediators. Previous studies suggest that miR155 may play adverse effects in various diseases. We hereby explored the roles of miR155 in the pathogenesis of Guillain-Barré syndrome (GBS). Peripheral blood mononuclear cells (PBMCs) were separated from GBS patients and healthy controls. Expression of miR155 in PBMCs was detected by quantitative PCR. An inhibitor of miR155 was transfected into the cultured PBMCs and the GBS-related cytokines were detected. Significantly, our study demonstrated that miR155 was downregulated in PBMCs from GBS patients and silencing of miR155 profoundly promoted the production of Th1-type cytokines in vitro. Our data effectively demonstrate a protective role of miR155 in GBS, which suggests that miR155 may be a promising target for the therapy of the disease.
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http://dx.doi.org/10.1007/s10753-012-9551-5DOI Listing
April 2013
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