A longitudinal and cross-sectional study of placental circulation between normal and placental insufficiency pregnancies.

INTRODUCTION: To longitudinally and cross-sectionally study the differences in the uterine artery pulsatility index (UTPI), umbilical artery pulsatility index (UAPI) and placental vascularization indices (PVIs, derived from 3-dimensional power Doppler) between normal and placental insufficiency pregnancies throughout gestation. METHODS: UTPI, UAPI and PVI were measured 6 times at 4- to 5- week intervals from 11 to 13+6 weeks-36 weeks. Preeclampsia (PE) and fetal growth restriction (FGR) were defined as placental insufficiency. Comparisons of UTPI, UAPI and PVI between normal and insufficiency groups were performed by one-way repeated measures analysis of variance. RESULTS: A total of 125 women were included: monitored regularly from the first trimester to 36 weeks of gestation: 109 with normal pregnancies and 16 with placental insufficiency. Longitudinal study of the normal pregnancy group showed that UTPI and UAPI decreased significantly every 4 weeks, while PVIs increased significantly every 8 weeks until term. In the placental insufficiency group however, this decrease occurred slower at 8 weeks intervals and UTPI stabilized after 24 weeks. No significant difference was noted in PVIs throughout pregnancy. Cross-sectional study from different stages of gestation showed that UTPI was higher in the insufficiency group from 15 weeks onward and PVIs were lower after 32 weeks. DISCUSSION: Compared to high-risk pregnancies with normal outcome, UTPI and UAPI needed a longer time to reach a significant change in those with clinical confirmation of placental insufficiency pregnancies and no significant change was found in PVI throughout gestation. UTPI was the earliest factor in detecting adverse outcome pregnancies.

The value of placental vascularization indices for predicting preeclampsia and fetal growth restriction in different stages of gestation: A prospective and longitudinal study.

INTRODUCTION: To assess value of placental vascularization indices (PVIs) for predicting preeclampsia (PE) and fetal growth restriction (FGR) in different stages of pregnancy in high-risk women. METHOD: PVIs derived from 3-dimensional power doppler(3DPD) imaging were measured at seven stages of pregnancy: 11-13+6w, 15-19+6w, 20-23+6w, 24-27+6w, 28-31+6w, 32-36+6w, and ≥37w. PE and FGR were used as outcomes in logistic regression models. Area under the receiver operating characteristic (ROC) curve (AUC) of each PVI was calculated, cut-off points were determined to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Finally, AUCs combined with baseline characteristics, uterine artery pulsatility index (UTPI) and PVIs were used to determine whether PVIs could increase the predictive value. RESULTS: Adverse outcomes occurred in 10.9% of pregnancies. Statistical differences appeared in 32-36+6w only. AUCs of vascularization index (VI) and vascularization flow index (VFI) for 32-36+6w were 0.79 (0.70-0.87, p: 0.000), and 0.78 (0.69-0.88, p: 0.000). Sensitivity, specificity, PPV, NPV, PLR, and NLR for VI were 0.91, 0.63, 20%, 98%, 2.39, and 0.15, and those for VFI were 0.62, 0.84, 29%, 95%, 3.75, and 0.45. AUC increased from 0.79 to 0.85 by adding PVIs to baseline characteristics and UTPI model. No statistical significance was found before 32w. DISCUSSION: VI and VFI were valuable for predicting PE and FGR at the 32-36+6w stage, while their values before 32w were poor.

[Clinical characteristics and outcomes of preoperactive short-acting octreotide treatment in patients with thyrotropin-secreting pituitary adenomas].

Objective: To explore the clinical characteristics of patients with pituitary thyrotropin-secreting adenoma and evaluate the effect of preoperative short-acting octreotide treatment on hyperthyroidism. Methods: A retrospective analysis was performed in 40 patients with pituitary thyrotropin adenoma diagnosed in Beijing Tiantan Hospital from January 2008 to January 2018. The general data, laboratory examinations and imaging findings were reviewed and analyzed. The clinical effect of preoperative octreotide on hyperthyroidism was evaluated. Results: The age of onset year of the 40 patients (male: female = 24∶16) was (30.5±5.1) years. Among them, 35 patients (87.5%) were with macroadenoma. The most common symptoms were thyroid hypermetabolism syndrome, followed by headache, dizziness, visual field damage and hypogonadism. The thyroid function of 30 patients (75%) recovered to normal within 3-5 days after the octreotide treatment. The total effective rate of the octreotide was 90.0%. The level of free thyroxine (FT4) before treatment in patients with more than 10 times of effective cumulative dose was significantly higher than that in patients with less than 10 doses. Conclusions: Thyroid hypermetabolism syndrome and pituitary occupying effect are the most common clinical manifestations of thyrotropin-secreting adenoma. Preoperative octreotide treatment can effectively control hyperthyroidism. The level of FT4 is a crucial factor affecting the efficacy of octreotide.

[Analysis of genotype and hematological phenotype of 14 patients with coinheritance HKαα and South-East deletion thalassemia].

Objective: To analyze the genotype-phenotype correlations among those thalassemia samples with the presence of -α(3.7,) --(SEA) and normal α(2) alleles on their α-globin gene clusters. Methods: Fourteen patients(including 1fetus, 4 males and 9 females, aged 0- 56 years old)who were suspected diagnosed by hematologic analysis and genetic testing among 16 080 participants in our laboratory since from August 2011 to August 2016, were enrolled. Complete blood cell count was performed on XE4000i automatic hemocyte analyzer. HbA0, HbF and HbA2 were tested by high performance liquid chromatography (HPLC). Gap-PCR was adopted to detect three common deletional thalassemia deletions. Reverse dot-blot (RDB) assay was applied for detecting 17 common ß-globin gene mutations and three common non-deletional α(2) gene mutations. Two-round nested PCR assay was established to detect the genotype of HKαα in α-thalassemia. Results: Fourteen cases were identified as HKαα/--(SEA) (14/16 080), including a pedigree and a rare case of HKαα/--(SEA) co-inheritance with IVS-Ⅱ-654(C→T) heterozygote. In HKαα/--(SEA) thalassemia group, mean cell volume(MCV) was (69.54±5.92)fl, and mean cell hemoglobin(MCH) was(22.11±2.22)pg and hemoglobin(Hb) was (117.64±18.14) g/L. Compared with normal group, MCV, MCH and Hb in HKαα/--(SEA) thalassemia group, was significantly decreased(P<0.05). There were no significant differences between α-thalassemia control group(--(SEA) /αα) in most hematological parameters (P>0.05). Conclusion: The two-round nested PCR could effectively detect the HKαα/--(SEA) genotype. The hematologic characteristics changed significantly in HKαα/--(SEA) group compared with HbH thalassemia and normal group. The genotype and phenotype non-correlation in patients with α-thalassemia should especially be causious to avoid a misdiagnosis of genetic tests, especially in prenatal diagnosis.

[Analysis of haematological phenotype and mutation spectrum of δ-globin gene from Guangdong area in Chinese Han prenatal population].

Objective: To analyze the genotype-phenotype correlations among southern Chinese Han prenatal population in Guangdong area with δ-globin gene mutation, so as to enrich the delta-thalassemia gene mutations data. Methods: A total of 33 cases were selected in 7 580 patients during prenatal thalassemia trait screening, from January 2012 to May 2015(including 10 males and 23 females, aged 22-48 years old). Complete blood cell count was performed on a XE 4000i automatic hemocyte analyzer. Hb, HbF and HbA2 were tested by high performance liquid chromatography (HPLC). Genomic DNA was extracted from whole blood samples using a whole blood genomic DNA extraction kit. Polymerase chain reaction (PCR) was used to amplify three different fragments corresponding to the exons and the regulatory sequences using three different couples of primers for the δ-globin gene. Results: Twenty one of the 33 samples were positive for the δ-globin gene defects. Four previously known mutations were detected: including 12 cases for -77(T>C)[HBD c. -127 (T>C)](57.14%), 4 cases for -30 (T>C)[HBD c. -80 (T>C)](19.05%), 1 case for codon 10 (-G) (HBD c. 31delG)(4.76%), and 1 case for HBD c. 244 C>T(4.76%). Three new δ-globin gene defects which had not yet been reported in database were detected, including 1 case for HBD c. 22_24delGAG(4.76%), 1 case for HBD c. 347 C>T(4.76%), and one case for HBD c. 349 C>G(4.76%). Conclusions: -77 (T>C) is the most common mutation in Chinese southern prenatal population. Three new HBD gene mutations are referred in this report, which provide the valuable information for genetic counseling and prenatal diagnosis in Guangdong area.

Combined effect of traditional Chinese and Western medicine on inflammatory factors in patients with diabetes-induced xerophthalmia.

Diabetes-induced xerophthalmia is a general metabolic disorder with high incidence and increased treatment difficulty. Our study aimed to explore the combined effect of traditional Chinese and Western medicines on diabetes-associated xerophthalmia. We recruited 60 diabetic xerophthalmia patients, and randomly assigned them to either the control (Western medicine treatment) or the experimental (combined treatment of traditional Chinese medicine and Western medicine) groups. Pre-treatment and post-treatment analyses were performed to assess the combined therapeutic effect of traditional Chinese and Western medicine on xerophthalmia-associated indicators. We found that the experimental group expressed reduced levels of IL-1, IL-8, and TNF-α (P < 0.05) as compared to the control group. Furthermore, the experimental group showed higher treatment efficacy as compared to the control group (85.00 vs 51.67% Z = 22.244, P < 0.05). In addition, break-up time (t = 20.582, P < 0.05) and tear section (t = 23.082, P < 0.05) was increased in the experimental group as compared to the controls. Lastly, it was found that the combined treatment of traditional Chinese and Western medicine effectively reduced corneal injuries, as indicated by reduced fluorescein staining. This study suggested that a combination treatment consisting of both traditional Chinese and Western medicines may be effective against xerophthalmia in diabetes, and that inflammatory factors are potential biomarkers to examine the treatment efficacy.

Rapid and sensitive LC-MS/MS method for the determination of auraptene in rat plasma and its application in a pharmacokinetic and bioavailability study in rats.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of auraptene, a constituent isolated from Fructus aurantii with potential to combat Alzheimer's disease, in rat plasma. Rat plasma samples were pretreated by protein precipitation with methanol. The analytes were separated by a Waters Sun Fire C18 column (50 mm x 2 mm, 5 µm) and eluted with 1:1000 methanol and formic acid/water (v/v) mobile phase with a flow rate of 0.5 mL/min. Multiple reaction monitoring was used to monitor the transition of the deprotonated auraptene molecule with an m/z of 299.3 [M+H](+), to the product ion with an m/z of 162.9 [M+H](+). Progesterone, with an m/z of 315.2→ 96.9 was used as an internal standard. The limits of detection and of quantification of auraptene in the rat plasma were 1 and 5 ng/mL, respectively. The method was linear in the concentration range of 20- 2000 ng/mL with coefficient correlation of 0.9956. After auraptene (100 mg/kg, p.o.) administration, the maximum plasma concentration and the time taken to reach maximum concentration were 1719.5 ± 384.3 g/mL and 108.0 ± 25.3 min, respectively. The elimination half-life was 108.0 ± 25.3 for auraptene (100 mg/kg, p.o.) and 3.0 ± 0 min for auraptene (2 mg/kg, i.v.). The oral bioavailability was about 8.5%.

[Effects of chrysin on sphere formation and CK2α expression of ovarian cancer stem-like cells derived from SKOV3 cell line].

OBJECTIVE: To investigate whether inhibitory effect of chrysin on sphere formation of ovarian cancer stem-like cells(spheroids derived from human ovarian cancer SKOV3 cell line ) is involved in the down-regulating of the protein expression of casein kinase CK2α. METHODS: SKOV3-derived ovarian cancer stem-like cells obtained by suspension culture in stem cell-condition medium using ultra-low adhesion plate were treated with various concentrations (5.0, 10.0 and 20.0 µmol/L) of chrysin. Sphere formation assay was used to determine the sphere forming rate of SKOV3-derived ovarian cancer stem-like cells. Western blot was used to analyze the protein expressions of CK2α and cancer stem cell markers CD133 and CD44. Silence of CK2α by siRNA and ectopic expression of CK2α by transfection with pcDNA3.1-CK2α plasmid were used to explore the mechanism underlying the effect of chrysin on sphere formation of SKOV3-derived ovarian cancer stem-like cells. RESULTS: Chrysin (5.0, 10.0 and 20.0 µmol/L) significantly reduced the sphere forming rate of SKOV3-derived ovarian cancer stem-like cells, in a concentration-dependent manner (22.3%±2.5% vs 14.7%±2.1%, 8.6%± 1.7% and 3.8% ± 1.1% respectively; P<0.05). In addition, chrysin (5.0, 10.0 and 20.0 µmol/L) obviously down-regulated the protein expressions of CK2α, CD133 and CD44 in SKOV3-derived ovarian cancer stem-like cells. In combination with CK2α siRNA transfection and chrysin synergistically decreased sphere formation (P<0.05) and the protein expressions of CK2α, CD133 and CD44 in SKOV3-derived ovarian cancer stem-like cells. However, transfection with pcDNA3.1-CK2α plasmid attenuated inhibitory effects of chrysin on sphere formation capability and the expressions of CK2α, CD133 and CD44 of SKOV3-derived ovarian cancer stem-like cells. CONCLUSION: Down-regulation of CK2α protein expression is involved in the inhibition effect of chrysin on the sphere formation capability of SKOV3-derived ovarian cancer stem-like cells.

Protective effects of melatonin against the damages of neuroendocrine-immune induced by lipopolysaccharide in diabetic rats.

The present study was to determine the protective effects of melatonin (MLT) against the damages of neuroendocrine-immune induced by lipopolysaccharide (LPS) in streptozotocin (STZ)-induced diabetic rats, and to analyze the parameters related to diabetes and oxidative stress. A total of 70 male Sprague-Dawley rats were assigned to this experiment. 10 of rats received STZ intraperitoneally (i.p.) alone as diabetic control; 40 of rats as the Diabetes+LPS received STZ plus LPS i.p. after induction of diabetes with STZ, then assigned to sub-groups as MLT (0.1) (mg), MLT (1) (mg), and Vehicle group, received two doses MLT and vehicle, i.p., respectively, q6 h for 12 h after LPS administration; and the remaining served as normal and LPS control. LPS significantly increased the serum levels of TNF-alpha and IL-6 in normal and diabetic rats; LPS also dramatically increased the plasma concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone. Both 0.1 and 1 mg/kg MLT doses significantly decreased the serum levels of TNF-alpha and IL-6. Significant inhibitory effects of MLT (1 mg/kg) were observed on the plasma concentrations of CRH, ACTH, and corticosterone of the HPA axis. The beneficial effects of MLT, such as the antioxidant activity and maintaining glucose homoeostasis, were also observed in this study, this resulted in a protective effect against the damages caused by LPS in STZ-induced diabetic rats. This finding probably provides a new approach for preventing the undesirable effects of the vicious cycle of hyperglycemia and stress factors such as severe infection in diabetic patients.

[Effect of three kinds (tonifying kidney, invigorating spleen, promoting blood circulation) recipes on the hypothalamus-pituitary-adrenal-thymus (HPAT) axis and CRF gene expression].

OBJECTIVE: To observe the effect of tonifying Kidney (TK), invigorating Spleen (IS) and promoting blood circulation (PBC) recipes on the hypothalamus-pituitary-adrenal-thymus (HPAT) axis. METHODS: Reverse-transcription polymerase chain reaction, radioimmunoassay and cellular immunity techniques were used to observe the effects of TH, IS, PBC on the neuroendocrine and immune system of this experimental model which HPAT axis was inhibited by corticosterone. RESULTS: Only TK could avoid the depression of exogenous corticosterone, which by enhancing the expression of CRFmRNA in hypothalamus, and following the improvement of function of HPAT axis, that IS might have direct promotion on immune system, whereas without any effect of PBC on HPAT axis was observed. CONCLUSION: TK, IS and PBC recipes have different effects on HPAT axis.