1.Advances of motor unit number estimation and motor unit number index in amyotrophic lateral sclerosis
Tianmi YANG ; Bei CAO ; Huifang SHANG
Chinese Journal of Neurology 2021;54(3):290-296
Amyotrophic lateral sclerosis (ALS) is a rapid progressive neurodegenerative disease, characterized by the degeneration of both upper and lower motor neurons. The progressive motor unit loss due to lower motor neuron damage is one of the most important pathological process in ALS. However, there are lack of specific biomarkers for early diagnosis and progression monitoring of ALS. The relevant electrophysiologic techniques which quantify the number of motor unit have been developed rapidly in recent years. Among them, the motor unit number estimation (MUNE) and the motor unit number index (MUNIX) have been widely applied to quantify motor unit number loss in ALS. The most recent advances of MUNE and MUNIX in ALS were reviewed.
2.Lysosomal trafficking regulator gene c.421C>T homozygous mutation causes adult Chediak- Higashi syndrome: one case report
Jiao LIU ; Shuying LI ; Xueping CHEN ; Huifang SHANG
Chinese Journal of Neurology 2021;54(5):491-495
The mutation of lysosomal trafficking regulator (LYST) gene and the clinical data of an adult patient who showed an abnormal gait with Chediak-Higashi syndrome were analyzed retrospectively. The whole exon sequencing was applied, and Sanger sequencing was used to verify the results. All members of the family were genetically verified for the same mutation site. The sequencing revealed the presence of c.421C>T(p.Arg141 *) mutation in LYST gene in the proband, which was inherited from his parents. The mutation was found in the homozygous state for the proband, both his parents being heterozygous for the same mutation. This mutation type was not reported in the human gene mutation database. According to the American Society of Medical Genetics and Genomic Society′s guide to the interpretation of genetic variation, the mutation of c.421C>T was identified to be pathogenic.
3.Influence of Coriaria Lactone on Ca2+-activated K+ channels in rat hippocampal pyramidal neurons
Xiaoyi ZOU ; Xiaohui LAI ; Huifang SHANG ; Shushun ZHOU ; Xiaorong ZENG ; Yan YANG
Chinese Journal of Tissue Engineering Research 2005;9(29):222-224
BACKGROUND: Electrical activity of nerve cells is based on the ion channel activity on cell membrane. Epilepsy is basically characterized by abnormal neuronal discharge. The foundation is ion channel activation on cell membrane and ion transmembrane movement, however, whether Ca2+-activated K+ channel involves in epilepsy induced by Coriaria Lactone is still unclear.OBJECTIVE: Considering rat hippocampal pyramidal neurons as target,we investigate the effect of Coriaria Lactone on neuronal Ca2+-activated K+ channels in epilepsy induced by Coriaria Lactone.DESIGN: Randomized controlled experimental trials.SETTING: Department of Neurology, West China Hospital, Sichuan University and Institute. of Myocardium Electrophysiology of Luzhou Medical College.MATERIALS: This experiment was carried out in Luzhou Medical College, Sichuan Province, from May to December 2000. Totally 100 Wistar infant rats within 24-hour ages were selected.METHODS: Wistar infant rats were anaesthetized and its hippocampus was obtained under disinfected state, pyramidal neurons were cultured for 7-10 days, neurons growing well with typical shape model were colleted normal control group, 19 dishes were added with DMEM culture medium,given different membrabe voltage and then followed by adding in te3 subgroups with 8 dishes each one. Added seperately DMEM culture medium containing f0-8, 10-7, 10~ mol/L concentration of calcium ion, and 2.0 mL/L Coriaria Lactone induced epilepsy group: added with DMEM culture medium with different dosages of Coriaria Lactone and finally tetraethylamine in each concentration of 26 dishes for totally 130 dishes.Cell-attache method and inside-out method of patch-clamp technique were used to record the neuronal single channel electricity. The open probability, average opening hour and closing hour, electric current amplitude of channel were analyzed.activated K+ channels of pyramidal neurons at normal, various membrane To observe and record the influence of Coriaria Lactone on the activation of pyramidal neuronal cell membrane, as well as the role of tetraethylamine.were only small amount of pyramidal neurons randomly opening its Ca2+-activated K+ channels and it displayed obvious voltage-dependent property.The channel electric conductance was (122.79±21.68) pS. The channels the inside-out condition, Ca2+-activated K+ channel displayed calcium iondependent property. The average opening rate was 0.022±0.006, 0.040±0.007, 0.142±0.049 when the calcium concentration was 10-8, 10-7,aria Lactone could increase the opening rate of Ca2+-activated K+ channels when the free calcium ion in bath solution was 10-8 mol/L and memLactone, 1.0 mL/L Coriaria Lactone could increase the average opening time of Ca2+-activated K+ channels (1.867±0.210, 6.900±0.120, P < 0.01), and reducing the average closing time (78.505±7.192,6.233±0.854, P < 0.01).CONCLUSION: In epilepsy induced by Coriaria Lactone, the activation of Ca2+-activated K+ channels might play an important role of negative modulation.
4.The efficacy and safety of autologous cryopreserved platelet transfusion in management of thrombocytopenia after chemotherapy in hematological malignancy
Guoqiang LIU ; Huifang DING ; Xifing LU ; Min XU ; Jian XING ; Xia ZHAO ; Fang HAN ; Yinghui SHANG
Chinese Journal of Internal Medicine 2012;51(3):188-191
Objective To investigate the efficacy and safety of autologous cryopreserved platelet transfusion in the management of thrombocytopenia after chemotherapy in hematological malignancy.Methods A total of 40 patients diagnosed as hematological malignancy with complete remission were equally assigned into study group and control group.During chemotherapy interval in the study group,when platelet counts exceeded 120 × 109/L,autologous platelets were collected with CS3000 Cell Separator and cryopreserved at-80℃ with 5% dimethylsulfoxide.When platelet counts dropped below 15 × 109/L after chemotherapy,autologous platelets were thawed with 40℃ water bath and transfused back to each patient.In the control group,when platelet counts dropped below 15 × 109/L after chemotherapy,allogeneic fresh platelets were transfused.Median loss during the freeze-thaw-wash procedure in study group was observed,and the 1 h,24 h corrected count increments(CCI)were calculated in the both groups.The hemostatic effects and adverse reactions were also observed.Results In the control group,1hCCI and 24hCCI were (19.3 ±6.1)× 109/L and(12.2 ± 7.0)× 109/L,respectively,with the effective rate of 80% and the transfusion reaction rate of 45%.Totally 20 collection and transfusions were finished in the study group.A total of(3.4-8.5)× 1011 platelet were obtained in each collection.Platelet recovery after freezing and thawing was(73.51 ±9.03)%(62%-83%).1hCCI was(17.4±7.6)× 109/L,24h CCI was(10.5 ±5.8)× 109/L and the effective rate was 85%.There was no significant different between the two groups (P > 0.05).The transfusion reaction rate was 15 %,which was significantly lower than that of the control group(P < 0.05).Meanwhile,adverse reactions were occurred less in the study group.Conclusion This study demonstrates that autologous cryopreserved platelet transfusions can be safely administered for supporting thrombocytopenia in hematological malignancy patients undergoing chemotherapy.
5. Progress in gene diagnosis of amyotrophic lateral sclerosis
Chinese Journal of Neurology 2020;53(1):50-54
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, for which early diagnosis is still very difficult up to now. With more and more ALS pathogenic and risk genes discovered, and especially the application of clinical trials of gene therapy in ALS, the genetic diagnosis becomes far more essential in ALS clinical practice. This presentation is a general introduction to the advantages and disadvantages of the commonly used gene detection methods, the key features of the pathogenic genes, the relationship between genotype and phenotype and the strategy of risk gene detection. The most common causative gene in Chinese ALS patients is superoxide dismutase (SOD1) gene, while in the Caucasian population is chromosome 9 open reading frame 72 (C9ORF72) gene. Familial ALS should be recommended for screening of ALS pathogenic gene panels. If negative, whole exome or genome sequencing is recommended to locate new pathogenic genes. The SOD1 and C9ORF72 should be routinely screened no matter in familial or sporadic form of ALS. In addition, if the patient has a special clinical phenotype, such as rapid or slow progression, cognitive impairment or extrapyramidal symptoms, genetic detection will be of great value for the diagnosis.
8.Mesenchymal stem cells increase platelet counts in mice with immune-mediated thrombocytopenia and affect T-bet and GATA-3 gene expression
Min XU ; Liang WANG ; Guoqiang LIU ; Guang LU ; Huifang DING ; Jian XING ; Xia ZHAO ; Fang HAN ; Yinghui SHANG
Chinese Journal of Microbiology and Immunology 2013;(11):828-832
Objective To explore the effects of mesenchymal stem cells ( MSC ) treatment on platelet counts in mice with immune-mediated thrombocytopenia ( ITP) and the possible mechanism .Meth-ods ITP was induced by daily intraperitoneal injection of anti-platelet membrane CD 41 antibody (MWReg30) into BALB/c mice.The mice were then divided into experiment and control groups with 20 mice in each.Each mouse in experimental group was injected with 2×107 mesenchymal stem cells (MSC) through the tail vein .The numbers of blood platelets in mice from two groups were counted on days 5, 7 and 14 after MSC injection .Reverse transcriptase polymerase chain reaction ( RT-PCR) was performed to meas-ure T-bet and GATA-3 gene expression in peripheral blood mononuclear cells ( PBMCs ) at mRNA level on day 14.The levels of IFN-γ, IL-2, IL-4 and IL-10 in serum were detected by ELISA .Results The platelet counts in experimental group were significantly higher than those in control group on days 7 and 14 after MSC injection [(588.0±81.6)×109/L and (623.0±78.9) ×109/L vs.(317.0±90.1) ×109/L and (288.0± 87.8)×109/L ] (P<0.05).On day 14 after MSC injection, the T-bet expression at mRNA level in PBMCs from mice in experimental group was significantly lower than that in control group [(0.04±0.03) vs.(0.27 ±0.05)] (P<0.05), while the GATA-3 expression at mRNA level was higher than those in control group [ (0.14±0.04) vs.(0.07±0.05)] (P<0.05).Compared with control group, the concentrations of Th1 type cytokines such as IFN-γand IL-2 were remarkably down-regulated in experimental group [(3.1±1.7) pg/ml and (3.2±2.1) pg/ml vs.(10.3±4.8) pg/ml and (16.3±5.7) pg/ml](P<0.05), while the con-centrations of Th2 type cytokines such as IL-4 and IL-10 were up-regulated in experimental group [(88.6± 15.2) pg/ml and (38.3±11.8) pg/ml vs.(32.7±5.7) pg/ml and (22.1±3.4) pg/ml ] (P<0.05). Conclusion MSC treatment can effectively increase platelet counts in mice with immune-mediated thrombo-cytopenia, which may be associated with the suppression of Th 1-dominant response mediated by abnormal ex-pression of T-bet and GATA-3.
9.Roles of exosomes in Parkinson's disease and amyotrophic lateral sclerosis.
Xiaojing GU ; Yongping CHEN ; Huifang SHANG
Chinese Journal of Medical Genetics 2018;35(5):757-761
Exosomes, as a kind of extracellular vesicles generated by inward budding of the endosomes to form multi-vesicular bodies (MVBs), are secreted into the extracellular milieu and the systemic circulation thereafter. By endocytosis, direct fusion or receptor-ligand interactions, exosomes can interact with receptor cells and involve in various pathophysiological processes. Accumulating evidence have indicated that exosomes may play crucial roles in the pathogenesis of many neurodegenerative diseases including Parkinson's disease (PD), Huntington's disease (HD), Alzheimer disease (AD) and amyotrophic lateral sclerosis (ALS). In this paper, the roles of exosomes in the pathogenesis, diagnosis and treatment of PD and ALS are reviewed.
10.Intellectual disability due to heterozygous c.40C>T variant of TRIP12 gene in a patient.
Jiao LIU ; Xueping CHEN ; Huifang SHANG
Chinese Journal of Medical Genetics 2021;38(2):131-133
OBJECTIVE:
To explore the genetic basis for a patient with intellectual disability.
METHODS:
Whole exome sequencing and Sanger sequencing were carried out for the patient. The result was verified in her family.
RESULTS:
DNA sequencing revealed that the patient has carried a heterozygous nonsense c.40C>T (p.Arg14X) variant of the TRIP12 gene, which was de novo in origin. The variant was unrecorded in the Human Gene Mutation Database. Based on the American College of Medical Genetics and Genomics standards and guidelines, the variant was predicted to be pathogenic (PVS1+ PS2+ PP3).
CONCLUSION
The patient was diagnosed with autosomal dominant intellectual disability due to heterozygous c.40C>T variant of the TRIP12 gene.
Carrier Proteins/genetics*
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Codon, Nonsense
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Female
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Heterozygote
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Humans
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Intellectual Disability/genetics*
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Ubiquitin-Protein Ligases/genetics*
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Whole Exome Sequencing