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1.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013430

ABSTRACT

Background Multiple studies have shown a close relationship between changes in gut microbiota composition and obesity, and research results are influenced by factors such as race and geographical location, but there are few studies on children. Objective To analyze the diversity of gut microbiota related to obesity in a population of 2-6 years old, observe the distribution characteristics and species differences of gut microbiota between obese/overweight and normal weight groups, and explore the association betweenobese/overweight and gut microbiota diversity. Methods Fecal samples were collected from 74 children aged 2-6 years in Shanghai, including 18 obese/overweight individuals, 6 males and 12 females (male to female ratio of 1∶2), and 56 normal weight individuals, 18 males and 38 females (male to female ratio is nearly 1∶2). The 16S rDNA was extracted from bacteria in fecal samples, followed by PCR amplification, cDNA construction, and high-throughput sequencing. Naive Bayes algorithm was used to perform taxonomic analysis (phylum, class, order, family, genus, species) and community diversity analysis (Sobs index, Shannon index, Shannoneven index, Coverage index, PD index, and principal co-ordinates analysis) on representative sequences and abundance of amplicon sequence variants (ASV). Wilcoxon rank sum test, P-value multiple test correction, and analysis of similarities were used to test differences between the two groups to obtain information on the distribution characteristics and species differences of intestinal microbiota in children. Results Seventy-four fecal samples were sequenced, and the sequencing results were subjected to quality control and filtering. A total of 4905306 optimized sequences were obtained, resulting in 1860 ASVs. The diversity data analysis of ASVs generated 889 species annotation results at 8 taxonomic levels. The alpha diversity analysis showed that the richness (Sobs index), diversity (Shannon index), evenness (Shannoneven index), and phylogenetic diversity (PD index) of fecal community of the obese/overweight children were increased compared to those of the normal weight children, but there were no statistical differences between the two groups (P>0.05). The beta diversity analysis showed that there was little difference in the composition of microbial species between the two groups, and no significant clustering separation was observed. The results of species composition analysis at phylum, order, family, and genus levels of 74 samples showed a consistent core microbiota structure in the two groups of gut microbiota, but there were differences in microbiota composition. The differences in microbial community composition between the two groups were manifested at the taxonomic levels of order, family, and genus, among which phylum Firmicutes, order Erysipelotrichales, family Erysipelatocyclostridiaceae, genus Erysipelotrichaceae_ UCG-003 and genus Catenibacterium were significantly enriched in the obese/overweight group and contributed significantly to the phenotypic difference of obese/overweight [linear discriminant analysis (LDA)=3.72, P<0.01; LDA=3.29, P<0.05). Phylum Proteobacteria, order Enterobacterales, family Enterobacteriaceae, genus unclassified was significantly enriched in the normal weight group and contributed significantly to the phenotypic difference of normal body weight (LDA=3.93, P<0.05). Conclusion The richness and diversity of gut microbiota in obese/overweight children aged 2-6 years in Shanghai are increased, but there is no difference compared to normal weight children. There is a difference in the composition of gut microbiota between the obese/overweight group and the normal weight group.

2.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1012659

ABSTRACT

ObjectiveTo explore the risk of different levels of pre-pregnancy obesity on trimester-specific thyroid dysfunction. MethodsQuestionnaire information, blood samples, and urine samples from a 2017 pregnancy cohort study in Shanghai, China were collected. A total of 2 455 pregnant women were included in the analysis. Pre-pregnancy BMI was calculated based on the height and self-reported pre-pregnancy weight. Serum TSH, total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3), thyroid globulin antibody(TgAb), and Thyroid peroxidase antibody (TPOAb) were measured using the electrochemiluminescence method. Urine iodine levels were measured using the acid digestion method. Levels of thyroid function indexes of pregnant women with different degrees of obesity during pre-pregnancy were compared, and trimester-specific thyroid dysfunction was evaluated according to the reference range of trimester-specific thyroid hormone established by this cohort. Multivariate logistic regressions analysis was used to assess the correlation between pre-pregnancy obesity and trimester-specific thyroid dysfunction. ResultsAs the degree of obesity increased, maternal levels of FT3 and TT3 gradually increased during pregnancy (P<0.001, P=0.001), while FT4 levels gradually decreased (P=0.001). Multivariate logistic regression analysis showed that compared with the normal weight group, pregnant women who were overweight or obesity before pregnancy had a significantly higher risk of hypothyroxinemia (OR=3.85, 95%CI: 2.08‒7.14, P<0.001) and high TT3 (OR=2.78, 95%CI: 1.45‒5.26, P=0.002) during pregnancy. ConclusionPre-pregnancy overweight or obesity can increase the risk of thyroid dysfunction during pregnancy.

3.
Chinese Acupuncture & Moxibustion ; (12): 1081-1085, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1007446

ABSTRACT

Acupuncture and moxibustion has certain advantages in the treatment of post-stroke spastic paralysis,but the treatment methods and diagnosis and treatment ideas are complicated. This paper sortes out the representative contemporary acupuncture and moxibustion schools in the treatment of post-stroke spastic paralysis, analyzes their academic origins,summarizes and compares the theory,acupoint selection and technique characteristics of different schools in the diagnosis and treatment of this disease,so as to provide some references for guiding optimal treatment schemes selection in clinic.


Subject(s)
Humans , Moxibustion , Muscle Spasticity/therapy , Acupuncture Therapy , Schools , Acupuncture Points , Stroke/therapy
4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1010171

ABSTRACT

OBJECTIVE@#To study epidemiological characteristics and hospitalization costs of female inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing.@*METHODS@#A retrospective study was conducted to analyze electronic hospitalization summary reports of female inpatients with AECOPD in Beijing from 2013 to 2020. Clinical characteristics (age distribution and comorbidities), epidemiological characteristics (temporal and spatial distribution characteristics), hospi-talization times and costs of patients were described.@*RESULTS@#A total of 57 911 subjects in 166 hospitals were included in this study, with a mean age of (78.84±8.59) years and the highest number of patients aged 80-89 years (49.06%), followed by patients aged 70-79 years (31.08%), and the lowest number of patients under 50 years (0.41%). The proportions of patients with coronary heart disease, hypertension and heart failure were 30.60%, 30.52% and 26.54% respectively. The median number of daily hospitalizations during the study period was 18 (IQR: 16). The number of daily hospitalizations for AECOPD showed an overall growth trend over the eight years from 2013 to 2020, starting to increase significantly in 2015 and continuing to increase until 2019, then followed by a decline in 2020. The proportion of inpatient admissions was higher in winter and spring (54.09%) than that in summer and autumn (45.91%). The top three districts in terms of the proportion of total inpatient admissions were Xicheng district (14.18%), Chaoyang district (14.12%) and Fengtai district (13.47%). The density of inpatients was relatively high in the western regions, central urban areas and northeastern regions of the city, while the density of inpatients was relatively low in the near suburbs. The median number of hospital days for female patients with AECOPD was 12 days, and the median hospital costs was CNY 20 648.37. Patients from urban areas had longer hospitalization times and higher hospitalization costs than those from suburban areas (P < 0.001). Western medicine expenses accounted for the largest proportion of total hospital expenses (33.32%). During the study period, hospitalization costs exhibited an overall pattern of initial growth, followed by subsequent decline, eventually stabilizing. The differences in hospitalization costs among the patients with different comorbidities were significant.@*CONCLUSION@#Female hospitalized patients with AECOPD in Beijing were older than 70 years, often complicated by cardiovascular disease. AECOPD occurred mainly in winter and spring, with regional differences. The hospitalization costs were closely associated with the patients' age, comorbidities, and the geographicical region.


Subject(s)
Humans , Female , Aged , Aged, 80 and over , Inpatients , Beijing , Retrospective Studies , Pulmonary Disease, Chronic Obstructive/epidemiology , Hospitalization
5.
Neuroscience Bulletin ; (6): 1157-1172, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-982467

ABSTRACT

Hv1 is the only voltage-gated proton-selective channel in mammalian cells. It contains a conserved voltage-sensor domain, shared by a large class of voltage-gated ion channels, but lacks a pore domain. Its primary role is to extrude protons from the cytoplasm upon pH reduction and membrane depolarization. The best-known function of Hv1 is the regulation of cytosolic pH and the nicotinamide adenine dinucleotide phosphate oxidase-dependent production of reactive oxygen species. Accumulating evidence indicates that Hv1 is expressed in nervous systems, in addition to immune cells and others. Here, we summarize the molecular properties, distribution, and physiological functions of Hv1 in the peripheral and central nervous systems. We describe the recently discovered functions of Hv1 in various neurological diseases, including brain or spinal cord injury, ischemic stroke, demyelinating diseases, and pain. We also summarize the current advances in the discovery and application of Hv1-targeted small molecules in neurological diseases. Finally, we discuss the current limitations of our understanding of Hv1 and suggest future research directions.


Subject(s)
Animals , Protons , Ion Channels/metabolism , Reactive Oxygen Species/metabolism , Brain/metabolism , NADPH Oxidases , Mammals/metabolism
6.
Article in English | WPRIM (Western Pacific) | ID: wpr-922759

ABSTRACT

Berberis amurensis (Berberidaceae) is a traditional Chinese medicine, which is often used to treat hypertension, inflammation, dysentery and enteritis. It contains alkaloids, mainly including berberine, berbamine, magnoflorine, jatrorrhizine and palmatine. Berberis amurensis extracts (BAEs) is often orally taken. Oral herbs might be metabolized by intestinal bacteria in the small intestine. However, the interaction between the herb and the gut microbiota is still unknown. In the current study, UPLC/Q-TOF-MS/MS combined with Metabolitepilot and Peakview software was used to identify the metabolites of BAEs in anti-biotic cocktail induced pseudo germ-free rats and normal rats. As a result, a total of 46 metabolites in normal rats were detected and its main metabolic pathways include demethylation, dehydrogenation, methylation, hydroxylation, sulfation and glucuronidation. Only 29 metabolites existed in pseudo germ-free rats. Dehydrogenated metabolites (M29, M30, M34 and M36), methylated metabolites (M33, M41 and M46) and other metabolites were not detected in pseudo germ-free rats. The result implied that the intestinal bacteria have an influence on the metabolism of BAEs. Furthermore, this investigation might contribute to the understanding of the metabolism of BAEs, and further promote its clinical application.


Subject(s)
Animals , Rats , Alkaloids , Berberis , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Tandem Mass Spectrometry
7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-905404

ABSTRACT

Objective:To investigate the effect of constant temperature blankets on intravascular hypothermia for severe traumatic brain injury (sTBI). Methods:A total of 112 inpatients with sTBI from January, 2013 to December, 2018 were reviewed. They were divided into control group (n = 58) and observation group (n = 54) according to whether a self-warming blanket was used. They were assessed with Bedside Shivering Assessment Scale (BSAS). Their dosages of anti-shivering medicine, coagulation and intracranial pressure were recorded. The scores of Glasgow Outcome Scale Extended (GOSE) and the mortality one, six and twelve months after discharge were observed. Results:The incidence and severity were less in the observation group than in the control group (χ2 = 16.212, P < 0.01). The dosage of anti-shivering medicine was less in the observation group than in the control group (t > 1.269, P < 0.05). The hypercoagulation relieved significantly six hours after hypothermia in the observation group, and it was stable twelve hours after hypothermia. For the control group, the hypercoagulation relieved significantly twelve hours after hypothermia, and it was stable 24 hours after hypothermia. The intracranial pressure decreased more in the observation group than in the control group. The GOSE score and the mortality were less in the observation group than in the control group (t > 1.168, P < 0.05) one, six and twelve months after discharge. Conclusion:Application of self-warming blankets in intravascular hypothermia for sTBI may relieve shivering, hypercoagulation and intracranial pressure, to improve the outcome of patients.

8.
International Eye Science ; (12): 865-868, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-820909

ABSTRACT

@#AIM: To compare the refractive outcomes of femtosecond LASIK with two different flap thickness in the correction of myopia.<p>METHODS: A total of 236 eyes of 118 myopic patients received LASIK with Wave-Light exeimer laser system. In the non-high myopia group, 30 people(60 eyes)used 90 micron corneal flaps, the other(60 eyes)used 110 micron corneal flaps; in the high myopia group,29 people(58 eyes)used 90 micron corneal flaps,the other(58 eyes)used 110 micron corneal flaps. Uncorrected distance visual acuity(UDVA), corrected distance visual acuity(CDVA), manifest refraction and intraocular pressure before operation, at 1mo, 3mo postoperatively were evaluated.<p>RESULTS: The percent of postoperative UDVA better than or equal to preoperative CDVA after 3mo: 57 eyes(95%). In the non-high myopia group no matter 90 micron corneal flaps or 110 micron corneal flaps. In the high myopia group, there are 53 eyes(91.4%)with 90 micron corneal flaps and 56 eyes(96.6%)with 110 micron corneal flaps(<i>P</i>=0.438); The percent of spherical equivalent refraction(SE)within ±0.50D of the target refraction change: 51 eyes(85%). In the non-high myopia group no matter 90 micron corneal flaps or 110 micron corneal flaps, 48 eyes(82.8%). In the high myopia group with 90 micron corneal flaps or 110 micron corneal flaps; The percent of change in SE within 0.50D between 1mo and 3mo postoperatively: there are 57 eyes(95%)with 90 micron corneal flaps and 55 eyes(91.7%)with 110 micron corneal flapsin the non-high myopia group(<i>P</i>=0.717). In the high myopia group, there are 44 eyes(75.9%)with 90 micron corneal flaps and 50 eyes(86.2%)with 110 micron corneal(<i>P</i>=0.464). <p>CONCLUSION: Both 90 micron corneal flaps and 110 micron corneal flaps show similar good efficacy, predictability and stability in the correction of myopia.

9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-777456

ABSTRACT

The Dendrobium species are rare and endangered medicinal plants, and it is difficult to investigate their wild resources with conventional methods because of typical epiphytic herbaceous. We explored Dendrobium resources(include culture resource) of Qinba Mountains and the boundary Mountain area in Hubei, Chongqing using the methods of literatures and field investigation, and found that the cultural base of Dendrobium were profound in Qinba Mountains region. Furthermore, its germplasm resources of Dendrobium were established for the first time in Wanzhou Luotian town. In case the advantages of local rock resources and poverty alleviation demand, we have actively carried out the cultivating mode of Dendrobium which grow on rock, and the poverty alleviation model of local characteristic Dendrobium industry were established preliminarily. Our application case can provide reference for the mining and transformation of traditional Chinese medicine resources census results.


Subject(s)
Agriculture , Economics , China , Dendrobium , Medicine, Chinese Traditional , Plants, Medicinal , Poverty
10.
Chinese Journal of Epidemiology ; (12): 461-465, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-805011

ABSTRACT

Objective@#To understand the homosexual behavior and related factors among married MSM in Mianyang city.@*Methods@#Between January and October in 2017, a snowball sampling method was adopted to carry out cross-sectional survey through questionnaires plus HIV testing among those MSM in Mianyang city. Logistic regression model was used to analyze homosexual behaviors and related factors among married MSM under study. Statistical analysis was used by EpiData 3.1 and SPSS 19.0 software.@*Results@#A total of 234 MSM participated in this survey. The overall rate of homosexual behavior in these married MSM appeared as 94.9% (222/234). Rate of having anal sex behavior was 94.4% (221/234) in the past 6 months, with rate of condom use as 57.9% (128/221). HIV positive rate was 8.1% (18/222). As for the motives for homosexual behavior after marriage, 87.8% (195/222) were driven by feelings of love, 12.2% (27/222) due to 'releasing pressure’. Proportion of male sex partners would include occasional sex partners (62.2%, 138/222), stable male sex partners (26.1%, 58/222) and stable boyfriends (11.7%, 26/222). Factors from logistic regression analysis showed that homosexual behaviors were related to the factors including education level of senior high school or above vs. education level of junior middle school or below (OR=3.65, 95%CI: 1.33-9.98); local residency over one year vs. the ones having local residency less than one year (OR=23.28, 95%CI:1.67-324.89); having 10 or more friends in the MSM community vs. having below 10 friends in MSM community (OR=4.15, 95%CI: 1.28-13.43); without sex pleasure with spouse vs. having sex pleasure with spouse (OR=3.25, 95%CI: 1.22-8.62); having 2 or more anal sex partners in the past 6 months vs. having less than 2 anal sex partners in the past 6 months (OR=0.28,95%CI: 0.09-0.81).@*Conclusions@#The rate of homosexual behavior and HIV positive rate were high among MSM in Mianyang city. Homosexual behaviors after marriage were influenced by multiple factors among MSM. The motives of homosexual behavior after marriage were driven by feelings of love, the related factors were education level of senior high school or above, local residency over one year, having 10 or more friends in the MSM community and without sex pleasure with spouse. As for the motives of these behaviors was caused by releasing pressure, the related factors was having more than 2 anal sex partners.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-816303

ABSTRACT

OBJECTIVE: To study the effects of Kushen gel on the growth of six common vaginal lactobacilli in vitro.METHODS: This study was conducted at Beijing Tsinghua Changgung Hospital from June 2018 to March 2019.Six different vaginal lactobacilli isolated from the healthy women of reproductive age in China were purified and cultured in vitro. The effect of different concentrations of Sophora flavescens alkaloid,which was the main active ingredient of Kushen gel,on the growth of various clinical lactobacillus isolates was observed by the agar dilution method.RESULTS: The minimum inhibitory concentration(MIC)of Sophora flavescens alkaloid to Lactobacillus rhamnosus was 40 mg/mL. The MICs for Lactobacillus crispatus,Lactobacillus jensenii,Lactobacillus gasseri and Lactobacillus reuteri were all 20 mg/mL. The MIC for Lactobacillus vaginalis was 10 mg/mL.When the concentration of Sophora flavescens alkaloid was lower than the MIC value,it had a certain effect on promoting proliferation of both Lactobacillus gasseri and Lactobacillus reuteri,but had no effect on Lactobacillus crispatus or Lactobacillus vaginalis.CONCLUSION: Under the clinical dosage,Kushen gel does not inhibit the growth of common vaginal lactobacilli,which is conducive to the recovery of the vaginal microecosystem.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-816201

ABSTRACT

OBJECTIVE: To explore the changes of normal vaginal micro-ecological environment after vaginal lavage with ozonated water and its effect on lactobacillus.METHODS: From April to October 2016,30 volunteers with normal vaginal microecological examination results were recruited from female workers in Beijing Tsinghua Changgung Hospital and selected to receive vaginal lavage with ozonated water,during non-menstrual periods 5 minutes per day,for 3 consecutive days.The vaginal secretions were taken before the first vaginal ozone lavage,the first week,the second week and the third week after the last lavage,and the microecological examination and the difference in the diversity and abundance of the vaginal microbial community were analyzed after 16 S rRNA high-through put sequencing.RESULTS: Before and after healthy women received ozone water for vaginal lavage,there were no significant differences in the microflora evaluation of vaginal secretions,vaginal microbial community diversity or lactobacillus(|cor. p| <0.2).CONCLUSION: Ozonated water for vaginal lavage does not destroy the normal vaginal microecology and has no significant effect on lactobacilli.

13.
Journal of Experimental Hematology ; (6): 1465-1470, 2018.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-689912

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the oxidative stress status and its effects on hepcidin in patients with hemoglobin H Constant Spring disease (HbH-CS).</p><p><b>METHODS</b>A total of 35 patients were enrolled in the study, including 15 splenectomized cases and 20 non-splenectomized cases. 20 healthy volunteers were selected as controls. Serum superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) levels, erythropoietin (EPO), serum free transferrin receptor (sFTR), growth differentiation factor 15 (GDF15) as well as the level of hepcidin were detected. Correlation analysis and multiple factor regression analysis were performed to investigate the factors affecting the iron metabolism and erythropoiesis.</p><p><b>RESULTS</b>Compared with healthy control, the SOD and GSH levels in patients with HbHCS decreased, while MDA and GSSG levels increased. The levels of SOD, MDA, GSG and GSSG were not significantly different between the patients with splenectomy and those without splenectomy. Correlation analysis showed that inpatients with HbHCS, EPO, sFTR and GDF15 correlated negatively with SOD level and positively with MDA level. EPO and sFTR levels negatively correlated with Hepcidin.</p><p><b>CONCLUSION</b>Excessive oxidative stress is present in patients with HbHCS, and hepcidin is inhibited by the upregulation of EPO and sFTR, and hence involved in iron overload in patients.</p>

14.
Journal of Experimental Hematology ; (6): 1800-1803, 2018.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-774383

ABSTRACT

OBJECTIVE@#To investigate the phenotype and genotype of the weak D blood group in one case of Chinese Han people.@*METHODS@#Phenotype of blood sample was identified with serologic tests; PCR-SBT was applied for the analysis of genotype and RhD zygosity.@*RESULTS@#Both saline and gel card tests demonstrated this case to be dCcee, which was contrary to glass bead card result. Some of the RBC D epitopes were negative.c.1022T>A allele was identified with PCR-SBT and the zygosity analysis showed this case to be D/d.@*CONCLUSION@#RHD*1022 A is more suitable to be categorized as weak partial D other than weak D in a Chinese Han people.


Subject(s)
Humans , Alleles , Asian People , Exons , Genotype , Phenotype , Rh-Hr Blood-Group System
15.
Neuroscience Bulletin ; (6): 992-1006, 2018.
Article in English | WPRIM (Western Pacific) | ID: wpr-775482

ABSTRACT

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the co-expression of molecular markers in epileptic human cortex. We found that parvalbumin (PV) and somatostatin (SST) neurons were distributed in all cortical layers except layer I, while tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were abundant in the deep layers and white matter. Cholecystokinin (CCK) neurons showed a high density in layers IV and VI. Neurons with these markers constituted ~7.2% (PV), 2.6% (SST), 0.5% (TH), 0.5% (NPY), and 4.4% (CCK) of the gray-matter neuron population. Double- and triple-labeling revealed that NPY neurons were also SST-immunoreactive (97.7%), and TH neurons were more likely to express SST (34.2%) than PV (14.6%). A subpopulation of CCK neurons (28.0%) also expressed PV, but none contained SST. Together, these results revealed the density and distribution patterns of different interneuron populations and the overlap between molecular markers in epileptic human cortex.


Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , Brain Chemistry , Genetics , Physiology , Cerebral Cortex , Metabolism , Pathology , Cholecystokinin , Metabolism , Epilepsy , Pathology , Gene Expression Regulation , Physiology , Interneurons , Metabolism , Neuropeptide Y , Metabolism , Parvalbumins , Metabolism , Phosphopyruvate Hydratase , Metabolism , Somatostatin , Metabolism , Tyrosine 3-Monooxygenase , Metabolism
16.
Neuroscience Bulletin ; (6): 237-246, 2018.
Article in English | WPRIM (Western Pacific) | ID: wpr-777063

ABSTRACT

N-methyl-D-aspartate receptors (NMDARs), a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2A (a gene encoding the NMDAR GluN2A subunit) mutations in patients with epilepsy. Phenotypes of GRIN2A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2A mutation (c.1341T>A, p.N447K) from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizure-free with a combination of valproate and lamotrigine. Functional investigation was carried out using recombinant NMDARs containing a GluN2A-N447K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293T cells revealed that the N447K mutation increased the NMDAR current density by ~1.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg inhibition. These results indicated that N447K is a gain-of-function mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue (N447A and N447E) did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447K as a novel mutation associated with epilepsy and validated its functional consequences in vitro. Identification of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.


Subject(s)
Adolescent , Humans , Male , Epilepsy, Rolandic , Genetics , Mutation , Receptors, N-Methyl-D-Aspartate , Genetics
17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-737190

ABSTRACT

Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide.Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression.Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases.Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs.Thus,we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9,Tregs and CHF.Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients.Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA),we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ-Ⅲ group were lower than that in NYHA grade Ⅳ group.More importantly,the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF),whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF.The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF.Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-735722

ABSTRACT

Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide.Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression.Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases.Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs.Thus,we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9,Tregs and CHF.Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients.Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA),we found that the HDAC9 mRNA expression level in NYHA grade Ⅱ-Ⅲ group were lower than that in NYHA grade Ⅳ group.More importantly,the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF),whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF.The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF.Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.

19.
Chinese Pharmacological Bulletin ; (12): 964-969, 2018.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-705160

ABSTRACT

Aim To study the effect of puerarin( Pue) against myocardial ischemia/reperfusion injury and in-volved mitochondrial mechanism. Methods Anoxia/reoxygenation( A/R) injury model was established in H9c2 cell. Recombinant plasmid pFLAG-VDAC1 was constructed. Cells were randomly divided into 4 groups, normal control group ( Control) , A/R group, puerarin group ( Pue + A/R ) , and pFLAG-VDAC1-Pue group. Real-time PCR was used to investigate the expression of VDAC1 at mRNA level, and the expres-sion of protein level was detected by Western blot. LDH and CK activities were measured by automatic bi-ochemical analyzer. Mitochondrial membrane potential ( Δψm) and cell apoptosis were observed by flow cy-tometry method. Mitochondrial swelling test was used to detect the opening of mitochondria permeability tran- sition pore ( mPTP) . Results Compared with control group, the expression of VDAC1 and mRNA was up-regulated in A/R group, LDH and CK activity were el-evated, and then mPTP opened, Δψm collapsed, cell apoptosis was significantly increased. Puerarin pre-treatment can lower the expression of VDAC1, main-tain Δψm, prevent the opening of mPTP, and reduce apoptosis. However, the protective effect of Puerarin could be cancelled by transfection of pFLAG-VDAC1. Conclusions The cardioprotection of Puerarin against A/R injury is closely related to down-regulation of VDAC1 and prevention of mPTP opening.

20.
Chinese Journal of Immunology ; (12): 492-495,501, 2018.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-702761

ABSTRACT

Objective:To investigate the impact of dexamethasone on the balance of natural regulatory T cells(nTreg) and typeⅠ regulatory T cell(Tr1) in vitro.Methods:Peripheral blood lymphocytes(PBMCs) recruited from healthy donor,divided into dexam-ethasone stimulus group and negative control group.After 3 days treatment,cells were stained.The expression of CD25,CD127, Lymphocyte-activation 3 (LAG-3) and Forkhead box P3 (Foxp3) and frequency of Treg and Tr1 were analyzed by flow cytometry.Results:Compared to the control group,after stimulation with dexamethasone for 3 days,the percentage of CD4+T cells increased in a dose-dependent manner.The expression of CD25 and Foxp3 in CD4+T cells decreased significantly (P=0.006, P<0.000 1),while CD127 and LAG-3 expression increased significantly in CD4+T cells (P<0.000 1,P=0.011).Dexamethasone treatment significantly enhance the frequency of Tr1(P=0.051),reduce the frequency of Treg (P<0.001),and the ratio of Tr1/Treg also increased(P=0.044).Conclusion:Short-term treatment with dexamethasone in vitro change the balance of natural regulatory and type Ⅰ regulatory T cells.

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