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Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer. This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405. 825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 [50%] vs 329 [40%]; relative risk [RR] 1·26, 95% CI 1·14–1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 [0·5%] in frozen single blastocyst transfer vs nine of 825 [1·1%] in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 [23·0%] vs 124 of 481 [25·8%]; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 [3·1%] vs four of 401 [1·0%]; RR 3·13, 95% CI 1·06–9·30, p=0·029). Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies. The National Key Research and Development Program of China.

Purpose To investigate the relationship of femoral head coverage (FHC) with Graf’s classification for diagnosis of developmental dysplasia of the hip (DDH) and its role in evaluating hip stability. Methods A total of 4222 hips were screened ultrasonographically with Graf’s and Harcke’s methods. The stability of hips was analyzed using the difference between FHCs at neutral and flexion positions (FHC-D). Results (1) For the non-dislocated hips, the mean value of FHC at the neutral position was 59.4%, which was significantly greater than 55.0% of FHC at the flexion position ( p  < 0.001). (2) FHC at the neutral position corresponding to Graf I, IIa/b, IIc, D, III, and IV was 63.0 ± 4.7%, 57.0 ± 5.2%, 49.5 ± 5.5%, 37.7 ± 3.7%, 30.2 ± 12.7%, and 7.4 ± 11.9%, respectively, and that at the flexion position was 59.0 ± 4.4%, 50.7 ± 9.4%, 35.2 ± 5.2%, 30.8 ± 1.3%, 23.4 ± 10.7%, and 4.7 ± 9.9%, respectively, showing a statistically significant difference between the two positions. (3) The AUC of FHC-D in evaluating the stability of hips was 0.972. When the threshold was 8.5%, the sensitivity, specificity, and accuracy of FHC-D in detecting hip instability were 89.0%, 93.0%, and 93.9%, respectively. Conclusions FHC can be used as a reference indicator for DDH classification. FHC at different positions corresponds to different reference values, and FHC-D can be used as a quantitative indicator for assessment of hip stability.

BackgroundGranulosa cell (GC) proliferation and apoptosis are critical events of the ovum energy supply, which lead to follicular growth retardation or atresia, and various ovulatory obstacles, eventually resulting in the development of ovarian disorders such as polycystic ovarian syndrome (PCOS). Apoptosis and dysregulated miRNA expression in GCs are manifestations of PCOS. miR-4433a-3p has been reported to be involved in apoptosis. However, there is no study reporting the roles of miR-4433a-3p in GC apoptosis and PCOS progression.MethodsmiR-4433a-3p and peroxisome proliferator–activated receptor alpha (PPAR-α) levels in GCs of PCOS patients or in tissues of a PCOS rat model were examined by quantitative polymerase chain reaction and immunohistochemistry. Bioinformatics analyses and luciferase assays were used to examine the association between miR-4433a-3p and PPAR-α, as well as PPAR-α and immune cell infiltration, in PCOS patients.ResultsmiR-4433a-3p expression in GCs of PCOS patients was increased. miR-4433a-3p overexpression inhibited the growth of the human granulosa-like tumor cell line (KGN) and promoted apoptosis, while co-treatment with PPAR-α and miR-4433a-3p mimic rescued miR-4433a-3p-induced apoptosis. PPAR-α was a direct target of miR-4433a-3p and its expression was decreased in PCOS patients. PPAR-α expression was also positively correlated with the infiltration of activated CD4+ T cells, eosinophils, B cells, gamma delta T cells, macrophages, and mast cells, but negatively correlated with the infiltration of activated CD8+ T cells, CD56+ bright natural killer cells, immature dendritic cells, monocytes, plasmacytoid dendritic cells, neutrophils, and type 1 T helper cells in PCOS patients.ConclusionThe miR-4433a-3p/PPAR-α/immune cell infiltration axis may function as a novel cascade to alter GC apoptosis in PCOS.

Abstract Context Women with obesity usually need larger doses of FSH for ovarian stimulation, resulting in poor outcomes; however, the mechanism is still unclear. Objective To investigate the molecular regulation of FSH receptor (FSHR) expression associated with obesity. Design Case-control study to improve in vitro fertilization (IVF) outcomes. Patients Women with obesity (82) and women who were overweight (457) undergoing IVF and 1790 age-matched controls with normal weight from our reproductive medicine center. Main Outcome Measures FSHR expression was decreased in parallel with body mass index (BMI), whereas the estradiol (E2) level on the human chorionic gonadotropin (hCG) trigger day was significantly lower. Results FSHR expression in human granulosa cells (hGCs), both mRNA (P = 0.02) and protein (P = 0.001) levels, was decreased in women who were overweight or obese. Both insulin (P < 0.001) and glucose (P = 0.0017) levels were positively correlated with BMI in fasting blood and follicle fluids (FFs) but not with FFs leptin level. We treated human granulosa-like tumor cells (KGN) cells with insulin; E2 production was compromised; the level of phosphorylated (p)-protein kinase B (p-Akt2) decreased, whereas p-glycogen synthase kinase 3 (GSK3) increased; and there were similar changes in hGCs from women with obesity. Stimulated hGCs from women with obesity with compound 21 (CP21), an inhibitor of GSK3β, resulted in upregulated β-catenin activation and increased FSHR expression. CP21 also increased the expression of insulin receptor substrate 1 and phosphatidylinositol 3-kinase (PI3K), as well as p-Akt2. Conclusions Women with obesity in IVF were associated with reduced FSHR expression and E2 production caused by a dysfunctional insulin pathway. Decreased FSHR expression in hGCs from women with obesity and insulin-treated KGN cells could be rescued by an inhibitor of GSK3β, which might be a potential target for the improvement of the impaired FSH-stimulation response in women with obesity. Obesity inhibits FSH receptor (FSHR) expression and estradiol production. Obese human chorionic gonadotropins and insulin resistance-modeled cells and compound 21 as an inhibitor of glycogen synthase kinase 3β could increase FSHR protein by the upregulation of β-catenin transcriptional activity.

Background Aneuploidy is one of the major factors that result in low efficiency in human infertility treatment by in vitro fertilization (IVF). The development of DNA microarray technology allows for aneuploidy screening by analyzing all 23 pairs of chromosomes in human embryos. All chromosome screening for aneuploidy is more accurate than partial chromosome screening, as errors can occur in any chromosome. Currently, chromosome screening for aneuploidy is performed in developing embryos, mainly blastocysts. It has not been performed in arrested embryos and/or compared between developing embryos and arrested embryos from the same IVF cycle. Methods The present study was designed to examine all chromosomes in blastocysts and arrested embryos from the same cycle in patients of advanced maternal ages. Embryos were produced by routine IVF procedures. A total of 90 embryos (45 blastocysts and 45 arrested embryos) from 17 patients were biopsied and analyzed by the Agilent DNA array platform. Results It was found that 50% of the embryos developed to blastocyst stage; however, only 15.6% of the embryos (both blastocyst and arrested) were euploid, and most (84.4%) of the embryos had chromosomal abnormalities. Further analysis indicated that 28.9% of blastocysts were euploid and 71.1% were aneuploid. By contrast, only one (2.2%) arrested embryo was euploid while others (97.8%) were aneuploid. The prevalence of multiple chromosomal abnormalities in the aneuploid embryos was also higher in the arrested embryos than in the blastocysts. Conclusions These results indicate that high proportions of human embryos from patients of advanced maternal age are aneuploid, and the arrested embryos are more likely to have abnormal chromosomes than developing embryos.

Polycystic ovary syndrome (PCOS) is the most common type of endocrine disorder, affecting 5-11% of women of reproductive age worldwide. Transcription factors (TFs) and microRNAs are considered to have crucial roles in the developmental process of several diseases and have synergistic regulatory actions. However, the effects of TFs and microRNAs, and the patterns of their cooperation in the synergistic regulatory network of PCOS, remain to be elucidated. The present study aimed to determine the possible mechanism of PCOS, based on a TF-microRNA synergistic regulatory network. Initially, the differentially expressed genes (DEGs) in PCOS were identified using microarray data of the GSE34526 dataset. Subsequently, the TFs and microRNAs which regulated the DEGs of PCOS were identified, and a PCOS-associated TF-microRNA synergistic regulatory network was constructed. This network included 195 DEGs, 136 TFs and 283 microRNAs, and the DEGs were regulated by TFs and microRNAs. Based on topological and functional enrichment analyses, SP1, mir-355-5p and JUN were identified as potentially crucial regulators in the development of PCOS and in characterizing the regulatory mechanism. In conclusion, the TF-microRNA synergistic regulatory network constructed in the present study provides novel insight on the molecular mechanism of PCOS in the form of synergistic regulated model.

Ovarian carcinoma is a common malignant disease worldwide with a poor therapeutic response. The present study investigated the effects of Na7CrCuW11O39.16H2O (CrCuW11) on ovarian cancer cell growth and investigated the mechanisms underlying its actions. The effects of CrCuW11 on cell viability and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, acridine orange/ethidium bromide staining and electron microscopy in human ovarian cancer SKOV3 cells. The expression of bcl-2-like protein 4 (Bax), B-cell lymphoma 2 (Bcl-2), cytochrome c, phosphorylated (p)-p38 and p38 was determined by western blot analysis. Caspase-3 activity was measured by caspase-3 activity kit. CrCuW11 concentrations of 1.87×10−3 mol. l−1 at 12 h reduced viability induced apoptosis in SKOV3 cells in a concentration-and time-dependent manner. Forced expression of CrCuW11 upregulated the expression of certain proteins (Bax, cytochrome c, and p-p38), and downregulated Bcl-2 protein expression. Furthermore, CrCuW11 also enhanced caspase-3 activity. The p38 inhibitor SB203580 was able to inhibit the activity of CrCuW11. Caspase-3 and p38 signaling pathways were associated with CrCuW11-regulated multiple targets involved in SKOV3 cell proliferation. Therefore, the results of the present study indicated that CrCuW11 may be used as a novel clinical drug for the treatment of ovarian cancer.

The sensing properties of semiconductive gas sensors originate from the resistance variation of depletion layer in each grain of the element. One of the most fundamental factors in this type of sensors is the width of depletion region. In this work, the antimony-doped tin oxide thin films for gas sensors are prepared via sol-gel routes on alumina substrates. The influence of antimony addition amount on electrical resistance of thin films is concluded. The relationship is plotted in the coordinates of logarithmic resistance against doping amount. On the basis of Schottky barrier model, a novel method is proposed to evaluate the width of depletion layer of semiconductive gas sensors by using the first order derivative of logarithmic resistance with respect to doping amount. Thus, the depletion layer width of the prepared antimony-doped thin film is calculated and its influencing factor is also discussed.

We study classical \\(J_1\\)-\\(J_2\\) models with distinct spin degrees of freedom on a honeycomb lattice. For the XY and Heisenberg spins, the system develops a spiral spin liquid (SSL) that is a thermal cooperative paramagnetic regime with spins fluctuating around the spiral contours in the momentum space, and at low temperatures supports a vector spin-chirality order despite the absence of long-range magnetic order. In a strong contrast, for the Ising moments, the low-temperature spin correlation forms a reciprocal \"kagomé\" structure in the momentum space that resembles the SSL behaviors and persists for a range of exchange couplings. The unexpected emergence and persistence of the reciprocal \"kagomé\" are attributed to the stiffness of the Ising moments and the frustration. At higher temperatures when the thermal fluctuations is strong and the spin correlation is not fully melted, the reciprocal structures evolve from the \"kagomé\" towards the ones demanded by the soft spin limit. This contrasts strongly with the behaviors of the spiral contours in the SSL regime for the continuous spins. We suggest various experimentally relevant systems including van der Waals magnets such as the transition metal phosphorus trichalcogenides TMPX\\(_3\\), Cr\\(_2\\)Ge\\(_2\\)Te\\(_6\\), the rare-earth chalcohalides (like HoOF, ErOF and DyOF) and other isostructural systems to realize the SSL-like behaviors and/or the reciprocal kagomé structure.

Apoptosis induction by short hairpin RNA (shRNA) expression vectors may be an efficient and promising strategy for cancer gene therapy. Ultrasound-targeted microbubble destruction (UTMD) is an appealing technique; however, there few data are available to demonstrate the feasibility and to optimize the methodology for this technology. The aim of this study was to optimize this technique and to elucidate the effects on gene inhibition and apoptosis induction in vitro. Human cervical cancer cell lines were obtained and cultured.shRNA vectors were constructed, and the UTMD technique was examined to determine whether or not it was suitable for shRNA transfection into cells. Cells were then examined using flow cytometry. The results revealed that the optimal irradiation parameters obtained higher transfection efficiency and did not affect the integrity of plasmid DNA. We concluded that survivin downregulation with shRNA expression vectors, mediated by the optimal UTMD parameters, markedly induced cell apoptosis and caused cell cycle arrest, laying a foundation for further investigation of this cancer therapy.