1.Roles of regulation of plasma cell function by Blimp1-B cell maturation antigen in the pathogenesis of systemic lupus erythematosus
Chinese Journal of Dermatology 2013;46(9):617-620
Objective To detect the expression of Blimp1 gene in MRL/lpr mice,so as to provide new ideas for plasma cell-targeting therapy of systemic lupus erythematosus (SLE).Methods Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation analysis (ChIP) were performed to evaluate the regulatory effect of Blimp1 on B cell maturation antigen (BCMA),and fluorescence-based quantitative PCR was carried out to detect the expression of Blimp1 mRNA in spleen and lymph node tissue of MRL/lpr mice and normal control mice.The intergroup difference in Blimp l mRNA expression was assessed by rank sum test.Results Blimp1 could bind to the BCMA gene promoter.Increased Blimp1 mRNA expression was observed in both the spleen and lymph node tissue of MRL/lpr mice compared with the normal control mice (Z =2.609,3.402,respectively,both P < 0.01).Conclusions BCMA appears to be the target gene of Blimp1,and Blimp1 may plays a certain role in the maintenance of plasma cell survival and antibody production via directly regulating BCMA gene expression.
2.The differences inexpressions of EGFR and VEGF between Han and Uygur triple-negative breast cancer patients
Weihua JIANG ; Yongtao LI ; Xiaowen WANG ; Mingshuai ZHANG ; Chenguang ZHANG ; Lina YI ; Jianghua OU
China Oncology 2016;26(5):404-408
Background and purpose:Triple-negative breast cancer (TNBC) is currently the focus of breast cancer research. Researches demonstrated that the molecular biological characteristics of different ethnic groups are not the same. This study mainly probed into the expression of endothelial growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in Han and Uygur TNBC patients, and the relationship between the expression and prognosis of patients.Methods:From Jan. 2007 to Jan. 2009, 167 patients were admitted. Among those, 121 were Han and 46 were Uygur patients. The expressions of EGFR, and VEGF were detected by PV-9000 immunohistochemical staining, and compared with lymph node metastasis and clinical staging. The results were analyzed by SPSS 18.0 statistical software.Results:Five-year disease-free survival (DFS) of two groups had no indifferent (P>0.05). EGFR and VEGF positive rate of Han patients was lower than that of Uygur patients (P<0.05). Their expressions were correlated with TNM staging and lymph node metastasis (0
3.Changes of thyroid autoantibodies and its relationship with dyslipidaemia in children with Turner syndrome
Wenqin LAO ; Zhe MENG ; Hui OU ; Lina ZHANG ; Lele HOU ; Zulin LIU ; Zhuannan JIANG ; Liyang LIANG
Chinese Journal of Applied Clinical Pediatrics 2017;32(8):579-581
Objective To investigate the changes of thyroid autoantibody(TAA)in children with Turner syndrome(TS),and its association between TAA and thyroid dysfunction,age,karyotype and dyslipidaemia.Methods Thirty-two patients with TS diagnosed by chromosome analysis hospitalized at Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University from July 2007 to July 2015 were divided into 2 groups based on TAA-positive or TAA-negative,then the thyroid dysfunction,the age,the karyotype and the lipid metabolism were compared between 2 groups.Results Of the 23 cases of TAA-positive girls(23/32 cases,71.88%),9 girls(39.13%)suffered from thyroid dysfunction;of the 9 cases of TAA-negative girls(9/32 cases,28.12%),3 girls(33.33%)had thyroid dysfunction.As compared with the girls in TAA-negative group,the age in TAA-positive group was significantly higher[(12.08±2.90)years old vs.(8.89±4.17)years old],and the difference was significant(t=101.500,P=0.047).The patients were divided into 4 age groups:0-5 years old,>5-10 years old,>10-15 years old and >15 years old;the rates with TAA-positive were 25.00%(1/4 cases),75.00%(6/8 cases),82.35%(14/17 cases)and 66.67%(2/3 cases)respectively.Twenty patients received the lipid metabolism test,and 11 cases(11/20 cases,55.00%)of them suffered from dyslipidaemia,9 cases of them were TAA-positive(9/11 cases,81.82%),and 2 cases were TAA-negative(2/11 cases,18.18%).The differences in the prevalence of dyslipidaemia between the 2 groups were significant(x2=4.848,P=0.028).There was no significant difference in the numbers of TAA-positive cases among different karyotypes(x2 =4.246,P=0.120).Conclusions Patients with TS are prone to suffer from thyroid dysfunction and dyslipidaemia.Timely detection of TAA and thyroid function is recommended,as well as the lipid metabolism if necessary.
4.The relationship of PALB2 and AR expression in triple negative breast cancer and its clinical significance
Weihua JIANG ; Mingshuai ZHANG ; Yongtao LI ; Xiaowen WANG ; Chenguang ZHANG ; Lina YI ; Laiti XUE ; Jianghua OU
The Journal of Practical Medicine 2017;33(9):1381-1384
Objective Discussion the relationship of PALB2 and AR expression in triple negative breast cancer and its clinical pathological features. Methods The SP immunohistochemical staining was adopted to detect the expression of PALB2 and AR in 178 cases of TNBC, PALB2 divided into two groups according to the expression of different, and to analyze the clinical pathological features and prognostic impact of different AR expression status. Results 178 cases of TNBC, that PALB2 missing expression 47 cases (26.4%), AR expression of 60 cases (33.7%), between of them were negatively correlated (-1≤r<1, P<0.05), in PALB2 negative group, AR expression associated with family history, lymph node metastasis, clinical stage and recurrence and metastasis (P<0.05), and 5-year disease-free survival lower than AR negative expression, Log rank = 4.453, P = 0.035. Conclusion PALB2 negative expression while AR positive expression in TNBC have synergistic effect with disease progression, PALB 2 and AR combined detection may provide a new basis for the prognosis of TNBC interpretation, and recommending take further studies to confirm.
5.Evaluation of the effect of different solutions for endoscopic nutrition in nasal and intestinal patients
Yufeng OU ; Huihua ZHAO ; Lina XU
Chinese Journal of Practical Nursing 2020;36(9):646-650
Objective:To investigate the effect of different solutions to prevent nasal intestinal blockage.Methods:Tottaly 199 cases of enteral nutrition treatment were selected from June 2018 to May 2019 and were randomly divided into three groups: warm boiled water group (67 cases), sugar-free cola group (67 cases), alpha-chymotrypsin group (65 cases). The rate of nasointestinal obstruction, the rate of nasointestinal obstruction, the rate of catheter patency maintenance, the rate of recanalization and the incidence of complications in three different enteral nutrition treatment cycles (< 7 days, 7-29 days, ≥ 30 days) were compared.Results:The catheter blockage rate in warm boiled water group was 20.9%(14/67) and in sugar-free cola group was 3.0%(2/67). The patency maintenance time in warm boiled water group was (8.83±1.84)days and in sugar-free cola group was (9.92±1.63) days ( t value was 2.182). The recanalization rate after blockage in warm boiled water group was 21.4%(3/14) and in sugar-free cola group was 100.0%( χ 2 value was 5.021, P < 0.05). The catheter blockage rate in sugar-free cola group was significantly lower than that in warm boiled water group, the catheter maintenance time and recanalization rate after blockage were significantly higher than that in warm boiled water group, the difference was significant ( P < 0.05). There was no significant difference between sugar-free cola group and alpha-chymotrypsin group in catheter blockage rate, catheter blockage rate, recanalization rate after blockage and incidence of complications( P > 0.05). The catheter blockage rate was 0 in patients with enteral nutrition treatment cycle < 7 days. The catheter blockage rate was 11.9%(8/67) (warm boiled water group) , 1.5%(8/67) (sugar-free cola group) and 1.5%(8/67) (alpha-chymotrypsin group) in patients with enteral nutrition treatment cycle 7-29 days. The catheter blockage rate was 9.0%(6/67) (warm boiled water group), 1.5%(1/65, sugar-free cola group) and 3.1%(2/67)(alpha-chymotrypsin group) in patients with enteral nutrition treatment cycle >30 days. The catheter blockage rate in sugar-free cola group and alpha-chymotrypsin group was significantly lower than that in warm boiled water group ( χ 2 values were 4.325-5.836, P<0.05) and there was no significant differences between the sugar-free cola group and the alpha-chymotrypsin group ( P>0.05). Conclusion:Sugar-free cola and alpha-chymotrypsin can effectively reduce the incidence of catheter blockage and complications, prolong the catheter patency and improve the recanalization rate after blockage, especially for patients with enteral nutrition treatment cycle longer than one week.
6.Analysis of clinical manifestations and gene mutations of 13 child patients with rare causes of primary adrenal insufficiency
Lele HOU ; Shaofen LIN ; Zulin LIU ; Hui OU ; Lina ZHANG ; Zhuannan JIANG ; Zhe MENG ; Liyang LIANG
Chinese Journal of Endocrinology and Metabolism 2019;35(1):15-20
Objective To analyze the clinical manifestations and gene mutations of rare causes of primary adrenal insufficiency (PAI) in childhood.Methods The clinical features,laboratory tests and gene mutation of 13 patients with PAI in our hospital from September 2010 to August 2017 were analyzed retrospectively.Patients with congenital adrenal hyperplasia,X-linked adrenoleukodystrophy with neurological onset or a clear family history,and autoimmune adrenal insufficiency were excluded.Results The median age of 13 cases (12 males,1 female) was 3 years and 10 months.Medical history or clinical manifestations on the first visit included hyperpigmentation,electrolyte imbalance/salt-wasting crisis,gastrointestinal symptoms,and fatigue,etc.All developments of external genitalia were normal.All cases presented with decreased serum cortisol and increased ACTH levels.Some of the cases showed decreased aldosterone level and plasma renin activity,while 17α-hydroxyprogesterone,testosterone,and androstenedione were in the normal range.Part of cases revealed delayed bone age and adrenal atrophy.Three gene mutations were detected in 13 patients,including NR0B 1 gene (9/13),ABCD 1 gene (3/13),and CYP 11A 1 gene (1/13).NR0B1,and ABCD1 gene mutations were pathogenic mutations,consistent with clinical characteristics.CYP11A1 gene mutation was heterozygote,which cannot fully explain the clinical features.Conclusion PAI in childhood presents common clinical manifestations of adrenal insufficiency,e.g.hyperpigmentation and electrolyte imbalance/sah-wasting crisis,but without specificity.Gene mutational analysis is necessary for precise diagnosis and prognosis estimation.NR0B1 and ABCD1 gene mutations were common in childhood with rare causes of PAI.
7.SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion.
Xiaolei LIU ; Biyan DUAN ; Zhaokang CHENG ; Xiaohua JIA ; Lina MAO ; Hao FU ; Yongzhe CHE ; Lailiang OU ; Lin LIU ; Deling KONG
Protein & Cell 2011;2(10):845-854
Bone marrow mesenchymal stem cells (MSCs) are considered as a promising cell source to treat the acute myocardial infarction. However, over 90% of the stem cells usually die in the first three days of transplantation. Survival potential, migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment. We hypothesized that stromal-derived factor-1 (SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes. In this study, apoptosis was induced by exposure of MSCs to H(2)O(2) for 2 h. After re-oxygenation, the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation. SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor. Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio. These protective effects were partially inhibited by AMD3100, an antagonist of CXCR4.We conclude that the SDF-1/CXCR4 axis is critical for MSC survival, migration and cytokine secretion.
Animals
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Apoptosis
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Apoptosis Regulatory Proteins
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genetics
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metabolism
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Bone Marrow Cells
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metabolism
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physiology
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Cell Hypoxia
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Cell Movement
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Chemokine CXCL12
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genetics
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pharmacology
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physiology
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Cytokines
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metabolism
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Gene Expression
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L-Lactate Dehydrogenase
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metabolism
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MAP Kinase Signaling System
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Male
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Mesenchymal Stem Cells
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metabolism
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physiology
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Proto-Oncogene Proteins c-akt
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metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, CXCR4
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metabolism
8. Analysis of the influence of iron overload in glucose metabolism in thalassemia major patients
Liyang LIANG ; Wenqin LAO ; Zhe MENG ; Lina ZHANG ; Lele HOU ; Hui OU ; Zulin LIU ; Zhanwen HE ; Xiangyang LUO ; Jianpei FANG
Chinese Journal of Pediatrics 2017;55(6):419-422
Objective:
This study aimed at determining the characteristics of the glucose homeostasis and its relationship with iron overload of the patients with β-thalassemia major (β-TM).
Method:
From Sun Yat-sen Memorial Hospital between January 2014 and December 2015, a total of 57 transfusion-dependent β-TM patients with 5-18 years old were enrolled in this study and fasting blood glucose(FBG) and insulin level, serum ferritin (SF), serum iron, transferrin, total iron binding capacity, unsaturated iron binding capacity were determined.Insulin resistance index (IRI), insulin sensitivity index and β-cell function index (BFI) were also estimated. Besides, in 36 patients cardiac T2* and liver T2* were estimated.
Result:
(1) Four patients(7%) with β-TM were diagnosed diabetes mellitus, and 14(24%) had impaired fasting glucose. (2) The incidence of abnormal glucose metabolism was significantly different according to levels of SF and degrees of the cardiac iron overload(χ2=9.737,
9.Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder.
Lulu PANG ; Siqing ZHU ; Jinqiu MA ; Lin ZHU ; Yijing LIU ; Ge OU ; Ruiteng LI ; Yaxin WANG ; Yi LIANG ; Xu JIN ; Lina DU ; Yiguang JIN
Acta Pharmaceutica Sinica B 2021;11(7):2031-2047
Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor-
10.Clinical and Genetic Study on 48 Children with Short Stature of Unknown Etiology
Lele HOU ; Shaofen LIN ; Xiaojuan LI ; Zulin LIU ; Hui OU ; Lina ZHANG ; Zhe MENG ; Liyang LIANG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):127-135
ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology, providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations, laboratory test and whole exome sequencing (WES) results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children (30 boys and 18 girls) were enrolled, aged 7.73 ± 3.97 years, with a height standard deviation score ( HtSDS) of -3.63 ± 1.67. Of the patients, 33 (68.8%) suffered from facial anomalies, 31 (64.6%) from skeletal abnormalities, 26 [54.2%, 61.5% of whom born small for gestational age (SGA)] from perinatal abnormalities, 24 [50.0%, 87.5% of whom with growth hormone (GH) peak concentration below normal] from endocrine disorders and 21(43.8%) had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was (9.72 ± 7.25) ng/mL, IGF-1 standard deviation score was -0.82 ± 1.42, the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES, 14 (56.0%) had pathogenic mutation, 6 (24.0%) likely pathogenic mutation, and 5 (20.0%) mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes, including 10 affecting intracellular signaling pathways (PTPN11, RAF1, RIT1, ARID1B, ANKRD11, CSNK2A1, SRCAP, CUL7, SMAD4 and FAM111A) and 4 affecting extracellular matrix (ECM) components or functions (ACAN, FBN1, COL10A1 and COMP). ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies, disproportionate body types, skeletal abnormalities, SGA, GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.