Dysregulated miRNAs contribute to altered placental glucose metabolism in patients with gestational diabetes via targeting GLUT1 and HK2.

INTRODUCTION: Dysregulated genes in glucose transport and metabolize pathways have been found in patients with Gestational diabetes (GDM), but the underlying mechanisms were still unclear. MATERIALS AND METHODS: Placental villous samples were collected from 31 patients with GDM and 20 healthy controls. The expression of GLUT1, GLUT4, GLUT9 and HK2 was examined by immunoblotting and qRT-PCR. The miRNAs have the potential targeting GLUT1 and HK2 were predicted using online bioinformatics tool: TargetScan. The interaction between miRNAs and target genes were confirmed by dual luciferase assay and immunoblotting. The function of miR-9 and miR-22 on glucose metabolism was examined by glucose uptake assay and lactate secretion assay. RESULTS: GLUT1 and HK2 proteins level was found upregulated in patients with GDM, but the mRNA level was not significantly changed. Predicted by using bioinformatics tools and confirmed by dual luciferase assay and immunoblotting, GLUT1 was identified as a target of miR-9 and miR-22, whereas HK2 was identified as a target of miR-9. MiR-9 and miR-22 level was found reduced in the placenta villous and negatively correlated with the expression of GLUT1 and HK2. Functional studies indicated that miR-9 and miR-22 inhibitors upregulated the expression of GLUT1 and HK2, and then increased the glucose uptake, lactate secretion, cell viability and repressed apoptosis in primary syncytiotrophoblasts (STBs) and HTR8/SVneo cells. DISCUSSION: The upregulation of GLUT1 and HK2 in the placenta, which is induced by miR-9 and miR-22 reduction, contributes to the disordered glucose metabolism in patients with GDM.

[Morbidity regularity of severe complications of hypertensive disorder complicating pregnancy in clinics].

OBJECTIVE: To analyse incidence of the severe complications of hypertensive disorder complicating pregnancy and the influence on the outcome of pregnancy. METHODS: A retrospective study of 4107 cases among 71 020 cases who delivered in hospitals from 1995 to 2004 in Guangzhou was conducted. RESULTS: The morbidity of hypertensive disorder complicating pregnancy was 5.78%, in which the morbidity of severe pre-eclampsia was 27.78% (1141/4107), of mitis pre-eclampsia was 72.22% (2966/4107). Maternal mortality rate was 0.19% (8/4107), and the specific mortality rate was 11.26/100 000. The proportion of severe complications of hypertensive disorder complicating pregnancy from high to low was as follows: placental abruption 1.68% (69/4107), DIC 1.36% (56/4107), hypertensive disorder complicating pregnancy induced cardiopathy (induced cardiopathy) 1.05% (43/4107), renal failure 0.97% (40/4107), cerebrovascular accident 0.58% (24/4107), and hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome 0.51% (21/4107). Mortality caused by severe complications of hypertensive disorder complicating pregnancy were as follows: cerebrovascular accident 17% (4/24), HELLP syndrome 10% (2/21), DIC 5% (3/56) and induced cardiopathy 2% (1/43). The proportion of perinatal mortality from severe complications were as follows: placental abruption 43% (33/77), HELLP syndrome 42% (10/24), DIC 34% (22/64), renal failure 25% (11/44), cerebro vascular accident 24% (6/25) and induced cardiopathy 16% (8/49). CONCLUSIONS: (1) The morbidity of severe complications from high to low are: placental abruption, DIC, induced cardiopathy, renal failure, cerebro vascular accident and HELLP syndrome. (2) The main causes of mortality for gravida and puerperant are: cerebro vascular accident, HELLP syndrome, DIC and induced cardiopathy. (3) The major complications harmful to perinatal newborns are in the order of: placental abruption, HELLP syndrome, DIC, renal failure, cerebro vascular accident and induced cardiopathy.

[Chorionic villus sampling for prenatal diagnosis: clinical analysis of 36 cases].

OBJECTIVE: To evaluate the safety and clinical value of chorionic villus sampling via the cervix for prenatal diagnosis of early pregnancy. METHOD: Thirty-six women with early pregnancy who required prenatal diagnosis received chorionic villus sampling via the cervix under the guidance by ultrasonography for laboratory examination of the samples. RESULTS: Villus sampling was performed successfully in 27 of the 36 cases in a single operation, whereas a second operation for sampling was needed in another 7 cases, with a total operation success rate of 94.4%;. The side effects included abdominal pain and vaginal bleeding in small quantity. In the 22 women who chose to continue the pregnancy, one woman experienced miscarriage at the 25th gestational week due to premature rupture of the membrane, and all other women gave birth to normal full-term infants. CONCLUSION: Chorionic villus sampling via the cervix under the guidance by ultrasonography is effective and safe for prenatal diagnosis in early pregnancy to help avoid induced abortion in mid-pregnancy and the occurrence of fetal defects.

[Intraoperative and postoperative risk factors for surgical site infection following cesarean section].

OBJECTIVE: To investigate intraoperative and postoperative high-risk factors for surgical site infection after cesarean section. METHODS: We retrospectively reviewed cesarean section cases in terms of emergency operation, anesthesia methods, operating time, blood loss, hospital stay, surgical skills of the surgeon, and postoperative nursing care to identify the high risk-factors of surgical site infection during and after the operation. A retrospective case-controlled study of all the parturients with postoperative surgical site infection was conducted. RESULTS: In the risk factors examined, anesthesia methods, operative time, and length of hospital stay showed significant differences between the two groups, while volume of blood loss and emergency operation did not. CONCLUSION: Effective measures need to be taken to eliminate the intraoperative and postoperative high-risk factors of surgical-site infection following cesarean section.

[Study of integrated state of HPV-16 infection in cervical cancer and precancerous tissues].

OBJECTIVE: To investigate the prevalence of physical state of HPV-16 DNA in cervical cancer and cervical precancerous carcinoma. METHODS: Multiplex PCR was adopted to detect the physical state of HPV in samples from 252 patients with cervical carcinoma, including 48 samples of cervical cancer, 204 cervical intraepithelial neoplasia (CIN ) (125 CIN I, 46 CIN II and 33 CIN III) and 20 normal samples from the subjects with hysteromyoma undergoing hysterectomy, respectively. RESULTS: Among 48 patients with cervical cancer, 31 (65.6%) were infected with HPV-16. Eighteen among 31 (58.1%) HPV-16 infected patients with cervical cancer were found to have integrated infection of HPV-16. The positive rates of HPV-16 infection in the patients with CIN I, CIN II and CIN III were 19.2%, 34.8% and 42.4%, and the integrated infection rates of HPV-16 were 16.7%, 18.8% and 35.7%, respectively. Compared with patients with different grades of CIN, the integrated rate of HPV-16 infection in those with cervical cancer was significantly elevated. CONCLUSION: Among the patients with HPV-16 infection, the integrated state of HPV-16 is positively correlated with the severity of cervical lesions. Combined HPV typing test and detection of integrated viral state contribute to predicting the prognosis of patients with cervical precancerous lesions and increasing the accuracy of screening cervical cancer on the basis of HPV DNA detection.

[Effect of heparin on fetal growth restriction].

OBJECTIVE: To investigate the clinical effect and safety of heparin in treating fetal growth restriction (FGR). METHODS: A total of 107 women diagnosed with FGR were randomized into three groups. Group 1 (standard heparin group, n = 37) received 50 - 75 mg standard heparin added to 500 ml 5% glucose sodium chloride, infused intravenously in 6 - 8 hours. Group 2 (low molecular weight heparin group, n = 31) received 0.2 - 0.4 ml low molecular weight heparin given by subcutaneous injection. Control group (n = 39) received 20 ml dan-shen added to 500 ml low-molecular-weight dextran infused intravenously. Fetal growth indices, biophysical score, umbilical artery blood flow, count of platelet (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), 1-minute Apgar score, body weight and gestational age of the neonates were measured. Babies prognosis was followed-up. RESULTS: (1) Height of fundus of uterus was obviously increased per week in the groups of standard heparin (0.7 +/- 0.6) cm and low molecular weight heparin [(0.7 +/- 0.6) cm]] vs. control group [(0.5 +/- 0.4) cm, P < 0.05]. Biparietal diameter of fetus increased in standard heparin [(2.4 +/- 0.7) mm] and low molecular weight heparin [(2.5 +/- 0.8) mm] groups vs. control [(1.7 +/- 0.6) mm, P < 0.05]. The femur length, head circumference and abdominal circumference of fetus were significantly longer in heparin treated patients than in control group (P < 0.05). (2) Biophysical score improved in groups of standard heparin (9.7 +/- 0.8) and low molecular weight heparin (9.6 +/- 0.6) vs. control group (8.9 +/- 0.7) (P < 0.05). (3) Umbilical blood S/D ratio decreased in standard heparin (2.5 +/- 0.5) and low molecular weight heparin (2.4 +/- 0.5) groups vs. control group (2.9 +/- 0.6) (P < 0.05). Pulsatile index (PI) and resistance index (RI) were significantly lower also (P < 0.05).(4) Rate of one minute Apgar score (8 - 10) was 86% in group 1, 87% in group 2 and 74% in control group, respectively. Body weight of the neonates was significantly increased in group 1(3100 +/- 256 g) and in group 2 [(3080 +/- 225) g] vs. [(2580 +/- 304) g] in control group (P < 0.05). Gestational age was prolonged in group 1 [(38 +/- 3) w] and group 2 [(38 +/- 4) w] vs. control group [(37 +/- 4) w, P < 0.05]. (5) Incidence of term small for gestational age infant in groups of standard heparin and low molecular weight heparin was 5% and 6%, respectively, significantly lower than those in the control group (18%) (P < 0.05). (6) No difference was shown in PLT, PT and APTT before and after heparin treatment (P > 0.05). (7) There was no difference in fetal growth indices, biophysical score, umbilical blood, neonatal outcome between standard heparin and low molecular heparin groups. CONCLUSIONS: Heparin can improve placenta function and obviously increase body weight of fetuses and neonates. It is safe for both pregnant women and their fetuses.

[Study on related factors of premature delivery and perinatal management].

OBJECTIVE: To study the etiological factors, perinatal management of premature delivery and the outcome of the premature infants. METHODS: The medical records of normal deliveries over the past 8 years in our hospital were respectively reviewed to analyze the difference between full-term and premature delivery cases in terms of maternal age, perinatal factors and manner of delivery. The states of birthing and outcomes of premature were reviewed. RESULTS: Preterm premature rupture of the membranes and in vitro fertilization-embryo transfer (IVF-ET) were the major causes of premature delivery, which was also related to such factors as placenta previa and pregnancy-induced hypertension. Premature delivery with unknown causes had been decreasing over these years. The maternal age and history of previous birth did not vary significantly between the full-term and the premature groups, but the later had significantly higher rates of cesarean section, in which 67.64% of the cases had Apgar scores

[Effect of heparin on umbilical blood flow in patients with fetal growth retardation].

OBJECTIVE: To investigate the effect of heparin on umbilical blood flow in pregnant women with fetal growth retardation (FGR). METHODS: A total of 103 FGR women were randomized into control group (n=37), standard heparin group (n=35) and low-molecular-weight heparin group (n=31). Low-molecular-weight dextran was given in the control group, and the other two groups received agents for intervention as indicated. The umbilical blood flow, 1-minute Apgar score, body weight and gestational age of the neonates were measured and compared between the 3 groups. RESULTS: As the gestational age increases, the systolic/diastolic (S/D) ratio, pulsatility index (PI) and resistance index (RI) were significantly lowered in the two heparin groups in comparison with those in the control group (P<0.05). One-minute Apgar score and body weight of the neonates were significantly greater in the two heparin groups (P<0.05), and the gestational age was also significantly longer (P<0.05). No statistical differences in the indices measured were noted between the two heparin groups (P>0.05). CONCLUSIONS: Heparin, which is safe for both the mothers and their fetuses, might improve fetal growth and development, increase neonate body weight, prolong the gestational age and raise the one-minute Apgar score.

[Expression of fragile histidine triad in endometriosis].

OBJECTIVE: To detect the expression of fragile histidine triad in endometriosis and investigate the pathogenesis of endometriosis. METHODS: immunohistochemistry was used to examine the expression of Fhit in the eutopic and ectopic endometria of 58 patients with endometriosis and in the endometria in 15 patients with hysteromyoma. RESULTS: The intensity of Fhit expression decreased in the order of normal endometrium, eutopic endometrium in endometriosis group, and ectopic endometrium. In patients with endometriosis, Fhit expression in the eutopic and ectopic endometria in proliferative phase showed no significant difference from that in secretory phase (P>0.05). Fhit expression in the ectopic endometrium showed significant difference between different r-AFS stages. MOD of ectopic endometrium in stages I-II was significantly higher than that in stages III-IV (P<0.05), but Fhit expression in the eutopic endometrium showed no significant difference (P>0.05). MOD of ovarian endometriosis showed no difference with that of adenomyosis. CONCLUSIONS: Fhit may play an important role in the development of endometriosis.

[Expression of ZNF217 in human ovarian cystadenocarcinoma and its clinical significance].

OBJECTIVE: To explore the correlation of ZNF217 expression to the carcinogenesis and progression of human ovarian cancer. METHODS: Immunohistochemistry and real-time RT-PCR were used to detect ZNF217 expression in human ovarian cystadenocarcinoma, ovarian cystadenoma and normal ovary tissues. RESULTS: The expression levels of ZNF217 protein and mRNA in ovarian cystadenocarcinoma was significantly higher than those in matched ovarian cystadenoma and normal tissues (P<0.05). No significant difference was found in the expression between ovarian cystadenoma and normal ovarian tissues (P>0.05). The mRNA expression in the specimens was consistent with the protein expression of ZNF217 (P<0.05). CONCLUSION: ZNF217 gene expression is closely correlated to the occurrence and clinical stages of ovarian carcinomas, suggesting that ZNF217 can be an important candidate gene responsible for the occurrence and progression of ovarian carcinomas.

[Ultrasonic study of deep-vein diameter and blood flow spectrum changes in full-term pregnant women].

OBJECTIVE: To explore the changes in lower limb deep vein diameters, blood flow velocity and blood biochemistry in full-term pregnant women for early diagnosis and treatment of prothrombotic state. METHODS: One hundred and twenty-eight full-term pregnant women at high risk of thrombosis (Group A), 61 healthy full-term pregnant women (Group B), and 42 healthy non-pregnant women (Group C) underwent high-resolution color Doppler ultrasound (CDU) for examining the deep veins of the lower limbs. The hematological indexes such as D-D, PLT, HGB, HCT, TT, APTT, PT, and FbgC were also observed in these 3 groups. RESULTS: Compared to Group B, the women in group A showed significantly increased diameters of the common femoral veins (CFV) and left superficial femoral vein (SFV), HCT and DD, but with significantly decreased peak blood flow in the bilateral popliteal veins (POPV) (P<0.01) and increased left POPV diameter (P=0.034). Compared to those in group C, the diameters of the bilateral CFVs, SFVs, POPV, and posterior tibial veins (PTVs) were significantly increased, but the peak blood flow in the bilateral CFVs and POPVs were significantly reduced in groups A and B; the PLT, HGB, HCT, DD, TT, APTT, PT, and FbgC also showed significant changes in groups A and B (P<0.01). CONCLUSION: The full-term pregnant women are at higher risk of prothrombotic state than non-pregnant women, and the full-term pregnant women with the high risk factors for thrombosis are more likely to have prothrombotic state than healthy full-term pregnant women. CDU examination of the lower limb deep veins can be of value in the diagnosis of prothrombotic state.

[Hysterectomy after cardiopulmonary resuscitation in patients with obstetric hemorrhagic shock].

OBJECTIVE: To explore the indication of hysterectomy after successful resuscitation of cardiac arrest due to obstetric hemorrhagic shock. METHODS: A retrospective analysis was conducted in 13 patients with cardiac arrest due to obstetric hemorrhagic shock in 7 hospitals of Guangzhou, including 12 patients undergoing hysterectomy and 1 undergoing uterine artery embolization. RESULTS: s After successful cardiopulmonary resuscitation, only 4 of the 13 patients undergoing hysterectomy or uterine artery embolization for continuing uterus hemorrhage survived. CONCLUSION: Detailed plans and emergency measures should be formulated in the management of high-risk pregnancies. Early diagnosis and active treatment of obstetric hemorrhagic shock with hysterectomy or uterine artery embolization are critical in preventing cardiac arrest and improving the survival of the patients.

[Clinical study of Osaka formula and improved multiparameter ultrasonic measurement for fetal weight estimation].

OBJECTIVE: To analyze the factors affecting the accuracy of Osaka formula multiparameter ultrasound-based fetal mass estimation, thereby establishing new formulas to improve the accuracy of the estimation. METHODS: A retrospective review was conducted among 519 healthy women with singleton pregnancy. Three days before the delivery (between 37 and 42 weeks' gestation), ultrasonic measurement of the fetal weight and other indices of the fetus was routinely performed. Correlation and multiple linear stepwise regression analysis were used to correct the 3 equations, which, along with Osaka University formula, were used to predict another 219 fetuses' birth weight. The coincidence rate of the predicted value and with the actual birth weight, and the absolute error and relative error were compared between the equations. RESULTS: The fetal abdominal area (AA) and abdominal circumference (AC) showed the most conspicuous influence on the estimated fetal birth weight, and fetal humerus length (HL) was more sensitive than femur length (FL) for the estimation. Three new regression equations were established, among which the equation 2 (fetal birth weight=1082.859+4.116xAAxHL) showed the best accuracy in clinical prediction. CONCLUSION: AA,AC and HL are more sensitive indices for estimation of the fetal birth weight, and the equation 2 established in this study still awaits further verification for its clinical value.

[Oncogene ZNF217 amplification on chromosome 20 q in ovarian serous cystadenocarcinoma and its clinical implications].

OBJECTIVE: To investigate the amplification of zinc finger protein 217 (ZNF217) gene on chromosome 20 in ovarian cancer and its clinical significance. METHODS: Twenty-three specimens of ovarian carcinoma (11 cases of early stage and 12 advanced stage), 10 specimens of benign ovarian tumors and 7 normal ovaries were examined for ZNF217 gene amplification on chromosome 20 by fluorescence in situ hybridization (FISH). RESULTS: ZNF217 gene amplification was detected in 12 cases of ovarian cancer (52.17%) and 1 case of benign ovarian tumor, but not in normal ovary. ZNF217 amplification was significantly associated with ovarian cancer. CONCLUSION: Oncogene ZNF217 is associated with the tumor stage and poor prognosis of patients with ovarian cancer.