1.The Relationship between Glycosylated Hemoglobin, Serum Visfatin Level and Perinatal Outcome in Pregnant Women with Normal Glucose Tolerance
Shaofang HUA ; Defeng KUANG ; Yuhuan HAN
Tianjin Medical Journal 2013;(10):953-956
Objective To investigate the relationship between the levels of serum glycosylated hemoglobin (HbA1c), serum visfatin, glucose and lipid metabolism and the perinatal outcome in pregnant women with normal glucose tolerance (NGT). Methods A total of 135 NGT pregnant women diagnosed by oral glucose tolerance test (OGTT) entered this study. Patients were divided into two groups, high HbA1c group (HbA1c≥5.5%, n=66) and normal HbA1c group (HbA1c<5.5%, n=69). The clinical data were collected in two groups. HbA1c levels were measured by HPLC, and the serum visfatin levels were measured by ELISA method. The values of body mass index (BMI), pregnant weight gain, visfatin, glucose and lipid met-abolic levels were analyzed between two groups. The relationship between levels of HbA1c, visfatin, glucose and lipid metab-olism and perinatal outcome were compared between two groups.Results The values of mean pregnancy weight gain, visfa-tin, total cholesterol (TC), triacylglycerol (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) were higher in high HbA1c group than those of normal HbA1c group. In NGT women with high HbA1c level,there were higher average birth weight, lower blood glucose level in newborn babies and higher rates of cesarean section. The incidences of polyhydram-nios, meconium-stained fluid, macrosomia and neonatal hypoglycemia were also higher in NGT women with high HbA 1c than those of normal HbA1c group. There was a positive relationship between HbA1c level, pregnant weight gain and visfatin and birth weight of newborn babies in 135 NGT pregnant women. Conclusion The excessive weight gain during pregnancy can induce the up-regulation of the visfatin level, resulting in the increased blood glucose level. The optimal timing and mode of delivery could prevent the occurrence of adverse pregnancy outcomes.
2.Expression of endoglin and transforming growth factor-β1 in placenta and superficial myometrium of women with gestational hypertension or preeclampsia
Junnong ZHANG ; Qunxing XU ; Yuhuan HAN ; Lijun ZHANG ; Shaofang HUA ; Wei DONG
Chinese Journal of Perinatal Medicine 2012;(12):732-736
Objective To investigate the expression of transforming growth factor-β1 (TGF-β1),endoglin (Eng) and their mRNA in placenta and superficial myometrium of patients with gestational hypertension or preeclampsia and to explore the role of Eng and TGF-β1 in the pathogenesis of gestational hypertension or preeclampsia.Methods One hundred and ten pregnant women were selected in the Second Affiliated Hospital of Tianjin Medical University from April 2009 to April 2010 who underwent cesarean sections and were divided into four groups:gestational hypertension group (n=30),mild preeclampsia group (n=30),severe preeclampsia group (n=30) and control group (normal pregnant women without labor and perinatal complications,n=20).The tissues of placenta and superficial myometrium were collected during cesarean section.Protein levels of Eng and TGF-β1 were detected by Western Blot.Real-time fluorescence reverse transcription polymerase chain reaction was used to detect the Eng and TGF-β1 mRNA expression.One-way ANOVA was used to compare among groups,Student-Newman-Keuls test was used to compare the differences between groups; relation between groups was analyzed by Pearson relation and linear regression.Results In control group,gestational hypertension group,mild and severe preeclampsia group,the Eng mRNA level was 1.00,1.27±0.58,1.54±0.41 and 1.83±0.35,and the TGF-β1 mRNA level was 1.00,1.64 ± 0.33,1.92± 0.38 and 2.23 ± 0.53 in placenta respectively; those figures changed to 1.00,1.32±0.46,1.59±0.37 and 1.93±0.52,and 1.00,1.71 ± 0.45,1.91 ± 0.51 and 2.37 ± 0.46 in superficial myometrium respectively.The Eng and TGF-β1 mRNA levels of control group were lower than those of the other three groups (P<0.05).The higher the mRNA level,the more severe the disease (P< 0.05).In control group,gestational hypertension group,mild and severe preeclampsia group,the Eng protein expression was 0.11±0.07,0.15± 0.05,0.18 ± 0.06 and 0.43 ± 0.04,and the TGF-β1 protein expression was 0.11 ±0.02,0.26 ± 0.05,0.27± 0.03 and 0.88 ± 0.09 in placenta respectively; those figures changed to 0.14±0.06,0.16±0.04,0.20±0.08 and 0.46±0.05,and 0.15±0.03,0.29±0.06,0.31±0.04 and 0.91 ±0.08 in superficial myometrium respectively.The Eng and TGF-β1 protein levels of control group were lower than those of the other three groups (P<0.05).The higher the protein level,the more severe the disease (P<0.05).In the gestational hypertension group,mild and severe preeclampsia group,there were positive correlations between Eng and TGF-β1 protein levels in placenta (r=0.57,0.61 and 0.60 respectively,P<0.05) and superficial myometrium (r=0.59,0.62 and 0.61 respectively,P < 0.05).Conclusions Eng and TGF-β1 might play a role in pathogenesis of gestational hypertension and preeclampsia.
3.Effects of soluble endoglin on nitric oxide production and nitric oxide synthase phosphorylation in cultured human umbilical vein endothelial cells
Wei DONG ; Qunxing XU ; Yuhuan HAN ; Lirong YIN ; Lijun ZHANG ; Shaofang HUA
Chinese Journal of Perinatal Medicine 2011;14(11):682-687
Objective To investigate the effects of soluble endoglin(sEng)on nitric oxide (NO)production and endothelial nitric oxide synthase(eNOS)phosphorylation in cultured human umbilical vein endothelial cells.Methods Human umbilical vein endothelial cells within 3 passages seeded in culture plates of 96 wells,were stimulated by total culture medium(control group)or sEng (1,10 and 100 μg/L)respectively.Cells and medium were collected after cells were cultured for 6,12 and 24 hours respectively.The concentration of the metabolites of NO in each group was measured by nitrate reductase method.The expression of eNOS and eNOS-Ser(p)1177 were detected by Western blot.The expression of eNOS mRNA in each group was detected by real-time fluorescence reverse transcription-polymerase chain reaction.Analysis of variance,LSD method and pearson correlation were used to compare the difference between groups.Results(1)The concentration of the metabolites of NO in 1,10 and 100μg/L sEng groups was(59.25±1.63),(41.08±2.71)and (30.38±1.63)μmol/L respectively after cultured for 6 hours;(54.98±3.34),(35.00±8.60)and (19.82±3.75)μmol/L for 12 hours; and(46.14±4.93),(30.24±2.08)and(12.78±5.01)μmol/L for 24 hours.There was no significant changes in control group with time going by(F=2.30,P=0.14).The concentration of the metabolites of NO was significantly lower in sEng group,and which had negative correlation with culture time(r=-0.98,P<0.05)and dose(r=-0.88,P<0.05).(2)The expression of eNOS in 1,10,100 μg/L sEng groups was 0.71 ± 0.00,0.47 ± 0.00 and 0.32±0.00 after cultured for 6 hours; 0.58±0.00,0.42±0.00 and 0.25±0.00 for 12 hours; and 0.49±0.00,0.33±0.00 and 0.18±0.00 for 24 hours.While the expression of eNOS and eNOS-Ser (p)1177/eNOS had no significant changes in control group with time going by(F=3.59 and 0.37,P=0.09 and 0.80).The expression of eNOS protein and eNOS-Ser(p)1177 decreased significantly in sEng groups,which had negative correlation with culture time(r=0.98 and-0.96,P<0.05)and dose(r=-0.76 and-0.79,P<0.05).(3)The expression of eNOS mRNA decreased significantly in sEng groups.Which also had negative correlation with culture time(r=-0.51,P<0.05)and dose(r=-0.82,P<0.05).Conclusions sEng might inhibit eNOS activity by blocking 1177 Ser phosphorylation to decrease NO production.
4. Effects of insulin therapy on skeletal muscle wasting in severely scalded rats and its related mechanism
Wanli CHU ; Jiake CHAI ; Xiaoteng WANG ; Shaofang HAN ; Lingying LIU
Chinese Journal of Burns 2019;35(5):333-340
Objective:
To explore the effects of insulin therapy on skeletal muscle wasting (SMW) in severely scalded rats and its related mechanism.
Methods:
Totally 48 male Wistar rats aged 7-8 weeks were divided into simple scald (SS) group and insulin therapy (IT) group according to the random number table, with 24 rats in each group. After weighing the body mass and measuring the blood glycemic level of the tail end with a glucometer, the rats in the two groups were immersed in hot water at 94 ℃ for 12 seconds to make a full-thickness dorsal scald model involving 30% total body surface area. Rats in group IT were subcutaneously injected with 1 U/kg insulin glargine at 8: 00 a day from post injury day (PID) 1 to 7, whilst rats in group SS were given the same amount of normal saline. Rats in the two groups were given 10 mL/kg enteral nutritional emulsion by intragastric infusion at 8: 00 (after insulin administration), 13: 00, and 18: 00 a day respectively from PID 1 to 7. The blood glycemic levels of tail end of rats in the two groups were measured by glucometer before insulin administration on PID 1-4, 6, and 7 and on every morning of PID 8, 9, 11, 12, and 14. The body mass of rats in the two groups on PID 14 without any treatment was weighed. Eight rats from each group were collected respectively on PID 4, 7, and 14 to harvest tibialis anterior muscle (TAM) samples. The mass of TAM on PID 14 was weighed. The ultrastructural changes of TAM myocytes on PID 7 were observed with transmission electron microscope. The apoptotic rates of TAM myocytes on PID 4, 7, and 14 were assessed by the assay of terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphate-biotin nick end labeling, the expressions of cysteine-aspartic protease-3 (caspase-3) of TAM on PID 4, 7, and 14 were detected with immunohistochemistry, and protein expressions of endoplasmic reticulum (ER) stress (ERS) associated proteins glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein-homologous protein (CHOP), and activated caspase-12 of TAM on PID 4, 7, and 14 were detected with Western blotting. Data were processed with completely random design
5.Analysis of the characteristics of SPTB gene variants among 16 children with Hereditary spherocytosis.
Yangyang GE ; Juanjuan LI ; Ye HAN ; Hua XIE ; Shaofang SHANGGUAN ; Qian JIANG ; Xiaoli CHEN ; Rong LIU
Chinese Journal of Medical Genetics 2023;40(3):269-275
OBJECTIVE:
To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation.
METHODS:
Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test.
RESULTS:
The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics.
CONCLUSION
Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.
Child
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Female
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Humans
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Male
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Computational Biology
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Genetic Testing
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Genomics
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Genotype
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Spherocytosis, Hereditary/genetics*
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East Asian People/genetics*
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Spectrin/genetics*
6.New research direction of organ dysfunction caused by hemorrhagic shock: mechanisms of mitochondrial quality control
Zheng ZHANG ; Hongjie DUAN ; Jiake CHAI ; Xiaofang ZOU ; Shaofang HAN ; Hailiang BAI ; Yufang ZHANG ; Huiting YUN ; Ran SUN
Chinese Critical Care Medicine 2024;36(1):93-97
Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.