Gonadotropin-releasing hormone agonist combined with hormone replacement therapy does not improve the reproductive outcomes of frozen-thawed embryo transfer cycle in elderly patients: a retrospective study.

BACKGROUND: With the rapid development of whole embryo freezing technology, more and more frozen-thawed embryo transfer (FET) was used in assisted reproductive technology. However, the best FET program for elderly women has not been finalized. We intended to explore the reproductive outcomes of traditional hormone replacement treatment and a gonadotropin-releasing hormone agonist (GnRHa) combined with hormone replacement treatment in the frozen-thawed embryo transfer cycle of elderly patients. METHODS: In this retrospective analysis, we analyzed 1264 elderly patients (aged 38 years or older) who underwent FET at three reproductive centers between 2015 and 2017. According to the endometrial preparation protocol, we divided the patients into a GnRHa combined with hormone replacement treatment (GnRHa-HRT) group and traditional hormone replacement treatment (HRT) group. The clinical pregnancy, ongoing pregnancy, live birth, and abortion rates were compared between groups. RESULTS: One-way analysis of variance of the two groups revealed no significant difference in the clinical (33.58% vs. 37.15%) and ongoing pregnancy rates (19.40% vs. 25.10%) between the GnRHa-HRT and HRT groups. The live birth rate (17.54% vs. 24.10% p = 0.0229) of the GnRHa-HRT group was lower than that of the HRT group, whereas the abortion rate (45.56% vs. 32.97% p = 0.0252) was higher than that of the HRT group. However, multivariate analysis showed no significant difference in the live birth rate (p = 0.1333) or abortion rate (p = 0.1881) between the GnRHa-HRT and HRT groups. The number of embryos transferred, level of the embryo, and age and ovarian reserve of the patient significantly affected final reproductive outcomes. CONCLUSION: A GnRH agonist combined with hormone replacement therapy did not improve the reproductive outcomes of frozen-thawed embryo cycles in elderly patients.

Synaptotagmin 1 regulates cortical granule exocytosis during mouse oocyte activation.

Synaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.

miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3ß in Alzheimer's disease.

As the most common neurodegenerative disease, Alzheimer's disease (AD) is characterized by memory, perception, and behavioral damage, which may ultimately lead to emotional fluctuation and even lethal delirium. Increasing studies indicate that microRNAs (miRNAs) are associated with pathological features of AD. However, the role of miR-219-5p in AD progression is still unclear. In this study, the functions of miR-219-5p were analyzed in vitro and in vivo. miR-219-5p was notably overexpressed in brain tissues of patients with AD. The overexpression of miR-219-5p activated the phosphorylation of Tau-Ser198, Tau-Ser199, Tau-Ser201, and Tau-Ser422. We further showed that miR-219-5p could mediate a decrease in the protein levels of tau-tubulin kinase 1 (TTBK1) and glycogen synthase kinase 3ß (GSK-3ß) by directly binding to their 3'-untranslated region, thereby promoting the phosphorylation of tau in SH-SY5Y Cells. Rescue experiments further revealed that the phosphorylation of tau-mediated by miR-219-5p was dependent on the inhibition of TTBK1 and GSK-3ß. Moreover, suppressing the expression of both TTBK1 and GSK-3ß using miR-219-5p remarkably rescued AD-like symptoms in amyloid precursor protein/presenilin 1 mice. Our findings indicate that the upregulation of TTBK1 and GSK-3ß mediated by the loss of miR-219-5p is a possible mechanism that contributes to tau phosphorylation and AD progression.

[Expression of long chain fatty acid oxidase in maternal and fetal tissues in preeclampsia-like mouse model in mid-gestation].

OBJECTIVE: To explore the protein expression and distribution of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) in various maternal and fetal tissues in preeclampsia-like and normal pregnant mouse models during the middle trimester. METHODS: C57BL/6J mice were divided into preeclampsia-like experimental group with Nw-nitro-L-arginine-methyl ester injection and normal pregnancy control group with normal saline injection. Samples were taken at Day 14 of gestation. Immunohistochemistry was used to detect the LCHAD protein expression and distribution in various maternal and fetal tissues. RESULTS: The mean arterial pressure was (115.6 ± 3.3) mmHg (1 mmHg = 0.133 kPa) in experimental group and (96.2 ± 4.9) mmHg in control group (P < 0.05). The urine protein contents were (97.0 ± 4.3) µg/g body weight/24h in experimental group and (60.8 ± 4.9) µg/g body weight/24h in control group (P < 0.05). In both groups, LCHAD protein was expressed in maternal liver, kidney, heart and placenta tissues during the middle trimester. And maternal hepatic tissue, myocardial tissue, renal tubule and spongiotrophoblast showed a strong positive expression, placental labyrinth layer a moderate positive expression and glomerulus a weakly positive expression. LCHAD expression of maternal liver and placenta decreased significantly in experimental group (P < 0.05). At Day 14 of pregnancy, LCHAD was expressed in fetal liver, kidney, heart, lung tissue and neural retina. And renal tubule, pulmonary epithelial tissue and neural retina showed a strong positive expression, fetal liver a moderate positive expression and myocardial tissue and glomerulus a weakly positive expression. There was no significant inter-group difference in fetal tissues. CONCLUSION: LCHAD is expressed and distributed widely in maternal and fetal tissues during the middle trimester. And it may play an important role in maternal metabolism and placenta-fetus development during pregnancy. There is an abnormal protein expression LCHAD in maternal liver and placenta with preeclampsia-like changes.

[Variation of long-chain 3-hydroxyacyl-CoA dehydrogenase DNA methylation in placenta of different preeclampsia-like mouse models].

OBJECTIVE: By detecting the variation of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) DNA methylation in preeclampsia-like mouse models generated by different ways, to explore the roles of multifactor and multiple pathways in preeclampsia pathogenesis on molecular basis. METHODS: Established preeclampsia-like mouse models in different ways and divided into groups as follows: (1) Nw-nitro-L-arginine-methyl ester (L-NAME) group: wild-type pregnant mouse received subcutaneous injection of L-NAME; (2) lipopolysaccharide (LPS) group: wild-type pregnant mouse received intraperitoneal injection of LPS; (3) apolipoprotein C-III (ApoC3) group: ApoC3 transgenic pregnant mouse with dysregulated lipid metabolism received subcutaneous injection of L-NAME; (4) ß2 glycoprotein I (ß-2GPI) group: wild-type pregnant mouse received subcutaneous injection of ß-2GPI. According to the first injection time (on day 3, 11, 16 respectively), the L-NAME, LPS and ApoC3 groups were further subdivided into: pre-implantation (PI) experimental stage, early gestation (EG) experimental stage, and late gestation (LG) experimental stage. ß-2GPI group was only injected before implantation. LCHAD gene methylation levels in placental were detected in different experimental stage. Normal saline control groups were set within wild-type and ApoC3 transgenic pregnant mice simultaneously. RESULTS: (1) CG sites in LCHAD DNA: 45 CG sites were detected in the range of 728 bp before LCHAD gene transcription start site, the 5, 12, 13, 14, 15, 16, 19, 24, 25, 27, 28, 29, 30, 31, 32, 34, 35, 43 CG sites were complex sites which contained two or more CG sequences, others were single site which contained one CG sequence. The 3, 5, 6, 11, 13, 14, 18, 28 sites in L-NAME, LPS, ApoC3 and ß-2GPI groups showed different high levels of methylation; the 16, 25, 31, 42, 44 sites showed different low levels of methylation; other 32 sites were unmethylated. (2) Comparison of LCHAD gene methylation between different groups: the methylation levels of LCAHD gene at 3, 11, 13, 14, 18 sites in L-NAME, LPS, ApoC3 and ß-2GPI groups were significantly higher than those in the normal saline control group (P < 0.05); and the methylation levels of 42, 44 sites in these groups were significantly lower than those in the normal saline control group (P < 0.05). (3) Methylation of LCHAD gene at the same site between different experimental stages: ① The 3, 11, 18 sites of EG experimental stage was significantly lower than PI and LG experimental stage in L-NAME group (P < 0.05); the 3, 11, 18 sites of PI experimental stage was significantly lower than EG and LG experimental stage in LPS group (P < 0.05); these sites of PI experimental stage was significantly higher than EG and LG experimental stages in ApoC3 group (P < 0.05). ② The methylation of site 5 in L-NAME and LPS groups were significantly higher than that of the normal saline control group (P < 0.05), and the LG experimental stages were significantly higher than other stages, but in ApoC3 group, only PI and EG stages were significantly higher than the normal saline control group (P < 0.05). ③ At site 6 in L-NAME group which showed high methylation level was significantly higher than the same site in other groups which showed low methylation level (P < 0.05). ④ At 13, 14 sites, earlier preeclampsia onset caused a lower methylation level in L-NAME group, but PI experimental stage was significantly higher than EG and LG experimental stages in LPS group (P < 0.05), EG experimental stage was significantly higher than PI and LG experimental stages in ApoC3 group (P < 0.05). ⑤ At site 28, earlier preeclampsia onset caused a higher methylation level in L-NAME group, but PI experimental stage was significantly lower than EG and LG experimental stages in LPS group (P < 0.05), EG experimental stage was significantly higher than PI and LG experimental stages in ApoC3 group (P < 0.05). ⑥ The 16, 25, 31 sites in ApoC3 group were significantly higher than other groups (P < 0.05). ⑦ At site 42 in ß-2GPI group was unmethylated, but it in other groups showed low methylation level, the methylation level of site 42 in ß-2GPI group was significantly lower than that in other groups (P < 0.05). CONCLUSIONS: The methylation of 6 and 42 CG sites may be related to LCHAD gene expression in placenta of L-NAME and ß-2GPI induced preeclampsia-like models respectively; LCHAD gene expression and DNA methylation may not have obvious correlation in LPS and ApoC3 induced preeclampsia-like models. Differences exist in LCHAD DNA methylation in preeclampsia-like models generated by different ways, revealed a molecular basis to expand our understanding of the multi-factorial pathogenesis of preeclampsia.

Sex differences in microstructural alterations in the corpus callosum tracts in drug-naïve children with ADHD.

Widespread alterations in the corpus callosum (CC) microstructure and organization have been found in children with attention-deficit/hyperactivity disorder (ADHD); however, few studies have investigated the diffusion characteristics and volume of transcallosal fiber tracts defined by specific cortical projections in ADHD, which is important for identifying distinct functional interhemispheric connection abnormalities. In the current study, an automated fiber-tract quantification (AFQ) approach based on diffusion tensor imaging identified seven CC tracts according to their cortical projections and estimated diffusion parameters and volume among 76 drug-naïve ADHD patients (53 boys and 23 girls) and 37 typically developing children (TDC) (20 boys and 17 girls) matched for age, IQ, and handedness. We found significantly lower fractional anisotropy (FA) in the occipital and superior parietal tracts and higher mean diffusivity (MD) in the posterior, superior parietal and anterior frontal tracts in children with ADHD compared with TDC. In addition, lower FA and higher radial diffusivity (RD) in the occipital callosal tract were significantly associated with higher hyperactivity and impulsivity performance in ADHD. In addition, sex-by-diagnosis interactions were observed in the occipital, posterior and superior parietal tracts. Girls with ADHD showed decreased FA and volume in the occipital tract, which were significantly associated with increased impulsivity performance and poor response control, and increased MD in the posterior and superior parietal callosal tracts, which were significantly associated with increased inattention performance, whereas boys with ADHD merely showed decreased volume in the frontal tract. Our results elucidated that sex-specific alterations in the CC tracts potentially underlie ADHD symptomatology and further suggested a differential contribution of abnormalities in different CC tracts to impulsivity and inattention among girls with ADHD.

Functional Connectivity of Attention-Related Networks in Drug-Naïve Children With ADHD.

Objective: This study aimed to explore alterations of seed-based functional connectivity (FC) in dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN) in ADHD children. Method: A voxel-based comparison of FC maps between 46 drug-naïve children with ADHD and 31 healthy controls (HCs) and correlation analysis between connectivity features and behavior were performed. Results: Compared with the HCs, children with ADHD were characterized by hyperconnectivity between DAN and regions of DMN and by hyperconnectivity between DMN and a set of regions involved in somatosensory, visual, and auditory cortices. No significant group different FC was found between VAN and the whole brain. Higher FC between DMN and somatosensory, visual, and auditory cortex was associated with better performance in attention and executive function. Conclusion: The dysregulation of networks in children with ADHD not only involves the DAN and DMN but also the somatosensory, motor, visual, and auditory networks.

[Quantitative determination of pinoresinol diglucoside in Eucommiae unloads by NIRS].

OBJECTIVE: To establish a rapid determination method of pinoresinol diglucoside in Eucommiae unloads by near-infrared reflectance spectroscopy (NIRS). METHOD: Forty-one samples of E. unloads were collected from three different producing areas and their main component, namely pinoresinol diglucoside, was determined by HPLC. Corresponding data of samples were collected from 12 000 to 4 000 cm(-1) by near-infrared reflectance spectroscopy. The spectral pretreatment was optimized by OPUS software and the calibration equations between the content of pinoresinol diglucoside and spectrum data were constructed by partial least squares regression. RESULT: Available information could be extracted from spectra in the range from 7 502 to 4 597.6 cm(-1) after corrected by applying second derivative transformation and subtract a linear correction. Cross validation was used to prevent over-fitting. Good correlation existed between pinoresinol diglucoside content and NIR spectra ( R2 = 0.926 4, SEC = 0.029 and SEP = 0.066 2). CONCLUSION: NIRS calibration equations developed in this study could be applied to the rapid analysis of the pinoresinol diglucoside content.

Aberrant white matter properties of the callosal tracts implicated in girls with attention-deficit/hyperactivity disorder.

Aberrant microstructure of the callosal tracts has been found in boys with attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether the previously identified white matter (WM) alterations in boys with ADHD are also present in girls with ADHD. Thus, we applied diffusion tensor imaging (DTI) to investigate WM alterations in the callosal tracts in girls with ADHD. In this study, twenty-four adolescent girls (fourteen ADHD patients and ten typically developed girls) were recruited for high-resolution DTI. Automated fiber quantification of the callosum forceps major and the callosum forceps minor was then conducted. Diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), were calculated to investigate the microstructural integrity of the two callosal tracts. We also investigated correlations between diffusion properties and clinical measurements, including scores on Conners' Parent Rating Scale, the Stroop Color-Word Test, the Wisconsin Card Sorting Test and the Continuous Performance Test, in ADHD patients and typically developed girls. Compared to typically developed adolescent girls, girls with ADHD had reduced FA values at nodes 59-70 and increased RD values at nodes 60-68 along the callosum forceps major. Lower FA values correlated with higher Hyperactivity-Impulsivity scores and lower control quotients, while higher RD values correlated with lower control quotients. This study revealed the disruption of interhemispheric connectivity, particularly across the right side of the occipital CC tract, which might be involved in visual processes in girls with ADHD. These findings enhanced current knowledge about the neuropathological basis of female ADHD.

Role of mammalian target of rapamycin signaling pathway in regulation of fatty acid oxidation in a preeclampsia-like mouse model treated with pravastatin.

BACKGROUND: Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several studies show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nω-nitro-L-arginine methyl ester (L-NAME) PE-like mouse model in our previous study. This study aimed to investigate the effect of mTOR signaling pathway in PE-like model treated with Pra. METHODS: Pregnant mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from gestational 7th to 18th day. Giving Pra (L-NAME + Pra, Control + Pra, n = 8) or normal saline (NS; L-NAME + NS, Control + NS, n = 8) from gestational 8th to 18th day, the mice were sacrificed on day 18 and their liver and placental tissues were collected. Then the activation of mTOR and its substrates in the liver and placenta were detected. And the association between mTOR activation and serum free fatty acid (FFA) levels and the expression of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) were evaluated using Pearson correlation test. Differences between groups were analyzed using independent t-test or one-way analysis of variance (ANOVA). RESULTS: Both in the maternal liver and placenta, the activation of mTOR protein and its effect on substrates increased significantly in the L-NAME + NS group and decreased significantly in the L-NAME + Pra group. The p-mTOR/mTOR protein ratio decreased in the L-NAME + Pra group significantly than that in the L-NAME + NS group both in liver and placenta (liver: 0.74 ±â€Š0.08 vs. 0.85 ±â€Š0.06, t = 2.95, P < 0.05; placenta: 0.63 ±â€Š0.06 vs. 0.77 ±â€Š0.06, t = 4.64, P < 0.05). The activation of mTOR protein in the liver and placenta negatively correlated with the expression of LCHAD in the L-NAME + NS group (liver: r = -0.745, P < 0.05; placenta: r = -0.833, P < 0.05) and that in the maternal liver negatively correlated with the expression of LCHAD (r = -0.733, P < 0.05) and positively with the serum FFA levels (r = 0.841, P < 0.05) in the L-NAME + Pra group. CONCLUSION: The inhibition of mTOR signaling pathway might be involved in the regulation of FAO in mouse model treated with Pra.

Different Effects of Pravastatin on Preeclampsia-like Symptoms in Different Mouse Models.

BACKGROUND: Pravastatin (Pra) exerts protective effects on preeclampsia. Preeclampsia is a multifactorial and pathogenic pathway syndrome. The present study compared the effects of Pra on clinical manifestations of preeclampsia in different pathogenic pathways. METHODS: Two different preeclampsia-like mouse models used in this study were generated with Nω-nitro-L-arginine methyl ester (L-NAME) and used lipopolysaccharide (LPS) from day 7 of gestation, respectively. Pra treatment was administered on day 2 after the models were established in each group (L-NAME + Pra, LPS + Pra, and Control + Pra, n = 8) or normal saline (NS) for the control group (L-NAME + NS, LPS + NS, and Control + NS, n = 8). Maternal weight, serum lipids, the histopathological changes, and lipid deposition in the liver and placenta were observed. The pregnancy outcomes were compared. The blood pressure analysis was carried out on repeated measurements of variance. Student's t-test was used for comparing the two groups. The enumeration data were compared by Chi-square test. RESULTS: The mean arterial pressure (MAP) and 24-h urinary protein in the L-NAME + NS and LPS + NS groups were significantly higher than the Control + NS group (F = 211.05 and 309.92 for MAP, t = 6.63 and 8.63 for 24-h urinary protein; all P < 0.05) and reduced in the L-NAME + Pra group as compared to the L-NAME + NS group (F = 208.60 for MAP, t = 6.77 for urinary protein; both P < 0.05). Urinary protein was decreased in the LPS + Pra group as compared to the LPS + NS group (t = 5.33; P < 0.05), whereas MAP had no statistical significance (F = 3.37; P > 0.05). Compared to the Control + NS group, the placental efficiency in the L-NAME + NS and LPS + NS groups decreased significantly (t = 3.09 and 2.89, respectively; both P < 0.05); however, no significant difference was observed in L-NAME + Pra and LPS + Pra groups (t = 1.37 and 0.58, respectively; both P > 0.05). Free fatty acid was elevated in the L-NAME + NS group as compared to the Control + NS group (t = 3.99; P < 0.05) at day 18 of pregnancy and decreased in the L-NAME + Pra group as compared to the L-NAME + NS group (t = 3.28; P < 0.05); however, no significant change was observed in the LPS model (F = 0.32; P > 0.05). CONCLUSION: This study suggested that Pra affected the clinical manifestations differently in preeclampsia-like mouse models generated in various pathogenic pathways.

Effects of Rapamycin on Clinical Manifestations and Blood Lipid Parameters in Different Preeclampsia-like Mouse Models.

BACKGROUND: The pathogenesis of some types of preeclampsia is related to fatty acid oxidation disorders. Rapamycin can regulate fatty acid metabolism. This study aimed to investigate the effects of rapamycin on the clinical manifestations and blood lipid parameters in different preeclampsia-like mouse models. METHODS: Two preeclampsia-like mouse models and a control group were established: L-NA (injected with Nω-nitro-L-arginine methyl ester), LPS (injected with lipopolysaccharide), and the control group with normal saline (NS). The mouse models were established at preimplantation (PI), early- and late-pregnancy (EP, LP) according to the time of pregnancy. The administration of rapamycin (RA; L-NA+RA, LPS+RA, and NS+RA) or vehicle as controls (C; L-NA+C, LPS+C, NS+C) were followed on the 2nd day after the mouse models' establishment. Each subgroup consisted of eight pregnant mice. The mean arterial pressure (MAP), 24-h urinary protein, blood lipid, fetus, and placental weight were measured. The histopathological changes and lipid deposition of the liver and placenta were observed. Student's t-test was used for comparing two groups. Repeated measures analysis of variance was used for blood pressure analysis. Qualitative data were compared by Chi-square test. RESULTS: The MAP and 24-h urinary protein in the PI, EP, and LP subgroups of the L-NA+C and LPS+C groups were significantly higher compared with the respective variables in the NS+C group (P < 0.05). The preeclampsia-like mouse models were established successfully. There was no significant difference in the MAP between the PI, EP, and LP subgroups of the L-NA+RA and L-NA+C groups and the LPS+RA and LPS+C groups. The 24-h urine protein levels in the PI and EP subgroups of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C groups (1037 ± 63 vs. 2127 ± 593 µg; 976 ± 42 vs. 1238 ± 72 µg; bothP < 0.05), also this effect appeared similar in the PI and EP subgroups of the LPS+RA and LPS+C groups (1022 ± 246 vs. 2141 ± 432 µg; 951 ± 41 vs. 1308 ± 30 µg; bothP < 0.05). The levels of serum-free fatty acid (FFA) in the PI and EP subgroups of the L-NA+RA groups were significantly lower compared with the respective levels in the L-NA+C group (2.49 ± 0.44 vs. 3.30 ± 0.18 mEq/L; 2.23 ± 0.29 vs. 2.84 ± 0.14 mEq/L; bothP < 0.05). The levels of triglycerides (TG) and total cholesterol in the PI subgroup of the L-NA+RA group were significantly lower compared with the respective levels in the L-NA+C (1.51 ± 0.16 vs. 2.41 ± 0.37 mmol/L; 2.11 ± 0.17 vs. 2.47 ± 0.26 mmol/L; bothP < 0.05), whereas high-density lipoprotein serum concentration was significantly higher (1.22 ± 0.19 vs. 0.87 ± 0.15 mmol/L;P < 0.05) and low-density lipoprotein serum concentration did not exhibit a significant difference. There were no significant differences in the FFA of the PI, EP, and LP subgroups between the LPS+RA and the LPS+C groups. The levels of TG in the PI subgroup of the LPS+RA group were significantly lower compared with the respective levels in the LPS+C group (0.97 ± 0.05 vs. 1.22 ± 0.08 mmol/L;P < 0.05). CONCLUSION: Rapamycin can improve clinical manifestations and blood lipid profile in part of the preeclampsia-like mouse models.

Decreased regional homogeneity in schizophrenia: a resting state functional magnetic resonance imaging study.

We used a newly reported regional homogeneity approach to measure the temporal homogeneity of blood oxygen level-dependent signal for exploring the brain activity of schizophrenia in a resting state. The results showed decreased regional homogeneity in schizophrenia, which distributed over the bilateral frontal, temporal, occipital, cerebellar posterior, right parietal and left limbic lobes, similar to the findings reported in previous resting state functional studies. The brain regions that showed decreased regional homogeneity are believed to be involved in the psychopathology and pathophysiology of schizophrenia. Our results indicate that abnormal brain activity of schizophrenia may exist in a resting state and the regional homogeneity may be potentially helpful in understanding the resting state of schizophrenia.

White matter integrity of the whole brain is disrupted in first-episode schizophrenia.

Diffusion tensor imaging studies in schizophrenia have demonstrated lower diffusion anisotropy within white matter that provides information about brain white matter integrity. We have examined whether white matter is abnormal in first-episode schizophrenia by using diffusion tensor imaging. Twenty-one schizophrenic patients and healthy controls underwent diffusion tensor imaging scans that analyzed by using a rigorous voxel-based approach. We found that fractional anisotropy in white matter of the patients was lower than that in controls at the cerebral peduncle, frontal regions, inferior temporal gyrus, medial parietal lobes, hippocampal gyrus, insula, right anterior cingulum bundle and right corona radiata. These results suggested that white matter integrity of the whole brain was disrupted in early illness onset of schizophrenia.

Adenosine Triphosphate Regresses Endometrial Explants in a Rat Model of Endometriosis.

The aim of this study was to determine the effects of adenosine triphosphate (ATP) in a rat endometriosis model. After surgical induction of endometriosis, 3 rats were killed, and explants were measured in the remaining 19 rats, which were then randomly assigned to 4 groups. Group 1 (n = 4) received normal saline (2 mL/d intragastric [IG]), group 2 (n = 4) gestrinone (0.5 mg/kg/d IG), group 3 (n = 5) ATP (3.4 mg/kg/d IG), and group 4 (n = 6) ATP (1.0 mg/kg/d; intramuscularly), respectively. Four weeks after medication, they were euthanized to evaluate histological features of explants and eutopic uterine tissues. To test the effect of ATP on the growth of eutopic endometrium stromal cells, proliferation rates of hEM15A cells at 24, 48, and 72 hours after treatment with different concentrations of ATP and vehicle control were detected with the Cell Counting Kit-8 (CCK-8) method. There was a significant difference between pretreatment and posttreatment volumes within group 2 (positive control; P = .048) and group 4 (P = .044). On condition that pretreatment implant size was similar in both groups (P = .516), regression of explants in group 4 was significantly higher than that in group 1 (negative control; P = .035). Epithelial cells were significantly better preserved in group 1 than in group 3 (P = .008) and group 4 (P = .037). The CCK-8 assay showed no significant difference in proliferation among hEM15A cells treated with ATP and controls. These results suggest that ATP regresses endometriotic tissues in a rat endometriosis model but has no impact on the growth of eutopic endometrium stromal cells.

Serum estradiol level change after human chorionic gonadotropin administration had no correlation with live birth rate in IVF cycles.

OBJECTIVE: To investigate the correlation between the estradiol (E2) level change after hCG administration and the live birth rate in GnRH agonist long or short protocols, and to explore the possible factors related to E2 dynamics after hCG administration during controlled ovarian hyperstimulation (COH). STUDY DESIGN: A retrospective analysis was performed on 2868 patients who received IVF/intracytoplasmic sperm injection (ICSI) treatment with GnRH agonist long or short protocol. The patients were divided into three groups according to their serum E2 changes after hCG administration, and the live birth rates were compared among groups. The area under the receiver operating characteristic (ROC) curve was calculated to assess the predictive value of E2 change for the probability of live birth. Logistic regression analysis was also applied to exclude interference from various confounding factors. Finally, multivariate regression analysis was conducted to assess factors related to the E2 change after hCG administration. RESULTS: No significant difference was observed in live birth rates (4.26%, 36.38% or 30.81% in long protocol (P=0.697); 25.81%, 26.71% or 30.81% in short protocol (P=0.697)) among patients with increasing, plateauing or decreasing E2 responses after hCG administration. The area under the ROC curve for the E2 change in prediction of live birth rate was 0.506 in long protocol, or 0.524 in short protocol. Logistic regression analysis showed that the serum E2 change after hCG administration had no correlation with live birth rate. Multivariate regression analysis showed that the percentage of mature follicles (larger than 14mm) and the duration of stimulation negatively correlated with the E2 change after hCG administration. CONCLUSIONS: In GnRH agonist cycles, the serum E2 change after hCG administration had no correlation with live birth rate in fresh embryo transfer cycles, and this change negatively correlated with the percentage of mature follicles on the day of hCG administration.

Premature progesterone rise negatively correlated with live birth rate in IVF cycles with GnRH agonist: an analysis of 2,566 cycles.

OBJECTIVE: To investigate the occurrence of premature progesterone rise (PPR) in GnRH agonist long or short protocol, address the relationship between circulating P levels and live birth rates, and explore the possible mechanism through which PPR affects clinical outcomes and the possible factors related to the occurrence of PPR. DESIGN: Retrospective analysis. SETTING: Reproductive medicine center of a public hospital. PATIENT(S): A total of 2,566 patients receiving in vitro fertilization/intracytoplasmic sperm injection treatment with GnRH agonist long or short protocol. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rates. RESULT(S): The corresponding incidence of PPR in long or short protocol was 22.86% (393/1,719) or 27.63% (234/847) with the cutoff value of 1.2 ng/mL or 2.0 ng/mL, respectively, being used to define PPR. Live birth rates decreased under the condition of PPR (40.65% vs. 29.77% in long protocol; 30.18% vs. 23.50% in short protocol). Logistic regression analysis showed that serum P level on the day of hCG administration was a strong predictor of live birth rate in both long and short protocols. Live birth rates in frozen embryo transfer cycles had no significant difference between groups with or without PPR (29.31% vs. 25.35% in long protocol; 24.84% vs. 24.22% in short protocol). Multivariate regression analysis showed that exogenous gonadotropin dose, the duration of stimulation, E(2) and LH levels on the day of hCG administration, the number of oocytes retrieved, and basal FSH level were all involved in PPR. CONCLUSION(S): In GnRH agonist cycles, PPR negatively correlated with live birth rate in fresh embryo transfer cycles, although no adverse impact on frozen embryo transfer was observed, implying that PPR may have deleterious effects on endometrial receptivity.