Objective To compare the outcomes of in-vitro maturation (IVM) and in-vitro fertilization (IVF) after early follicular phase gonadotropin-releasing hormone agonist (GnRH-a)down-regulation in infertile patients with polycystic ovary syndrome (PCOS).Methods From July 2010 to December 2012,72 infertile patients with PCOS undergoing assisted reproductive technology treatment in the Affiliated First Hospital of Wenzhou Medical University were enrolled in this study.The patients were divided into 2 groups,which were patients with early follieular phase down-regulation IVM (36 cases) at IVM group and early follicular phase down-regulation long protocol IVF (36 cases) at IVF group.The laboratory parameters and clinical outcomes were compared between two groups.Results (1) Lab parameters:a total of 442 oocytes were retrieved in group IVM,and 560 were in group IVF.The rate of mature oocytes of 83.8％ (469/560) and high-quality embryos of 70.9％ (212/299) at group IVF were significantly higher than that of group IVM [54.1％ (239/442) and 50.7％ (73/144),retrospectively,P ＜0.01].In group IVM,the average duration of gonadotropin (Gn) was (2.8 ± 1.5) days and the average dosage of Gn was (285 ± 169) U,which were significantly lower than (11.0 ± 1.0) days and (1499 ±165) U in group IVF (P ＜0.01).The mean number of oocytes retrieved 12.8 ± 2.5,fertilization rate of 64.8％ (155/239),and implantation rate of 31％ (23/74) in group IVM and 15.6 ±3.1,65.5％ (307/469),31％ (23/74) in group IVF,which did not reach statistical difference (P ＞0.05).(2) Clinical outcomes:the clinical pregnancy rate (17/31,55％) of IVF group was not significantly higher than that 44％ (14/32) at IVM group (P ＞ 0.05).The abortion rate was 1/17 at Group IVF and 1/14 in group IVM,which did not show statistical difference.Women at IVM group has no ovarian hyper-stimulation syndrome (OHSS) cycle,group IVF has 31％ (11/36) cycles presented moderate and severe OHSS.Conclusions Infertile patients with PCOS undergoing IVM and IVF treatment after early follicular phase GnRH-a down-regulation can get satisfactory laboratory and clinical outcome.In addition to short treatment cycle,IVM can also avoid the occurrence of OHSS completely,but it has a rising trend in the abortion rate.IVF has a high incidence of OHSS,meanwhile,it increases the dosage of gonadotropins.

AIM: To observe the effect of osthole on tricalcium phosphate (TCP) particles-induced calvarial osteolysis in vivo.METHODS:Male ICR mice were randomly divided into sham group , TCP group and osthole group .A mouse calvarial model of osteolysis was established by TCP particles .On the second postoperative day , osthole (20 mg/kg) was locally injected into the calvarium under the periosteum 3 times a week.Two weeks after osthole treatment , blood and calvaria were collected to determine the level of bone turnover markers such as alkaline phosphatase ( ALP) , osteocalcin and tartrate-resistant acid phosphatase ( TRACP) .The periosteum was performed to examine the release of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and IL-1βby ELISA.The calvaria was obtained for histological and molecular analyses.RESULTS:Data from HE and TRACP staining revealed that osthole prevented TCP particles-induced obvious increase in osteoclastogenesis and resorption area in the metaphysis of mouse calvaria .Osthole treatment increased ALP ac-tivity and osteocalcin level , and dncreased the activity of TRACP in the mouse serum compared with TCP group .Further-more, TCP particles-induced the releases of TNF-α, IL-6 and IL-1βwere significantly suppressed by osthole treatment .In addition, Western blot demonstrated that endoplasmic reticulum ( ER) stress markers such as glucose-regulated protein 78 (GRP78) and CAAT/enhancer binding protein homologous protein (CHOP) were significantly up-regulated in TCP parti-cles-implanted calvarial mice , indicating that TCP particles triggered an ER stress response in the mouse calvarial osteolysis model , which obviously attenuated by osthole .CONCLUSION:Osthole inhibits TCP particles-induced calvarial osteolysis in mice, which is mediated by inhibition of ER stress signaling pathway .

Objective To compare the laboratory and clinical results between unstimulated in vitro maturation (IVM) and IVM converted from in vitro fertilization (IVF) in polycystic ovarian syndrome (PCOS) and non-PCOS patients.Methods We divided 591 IVM cycles in the First Affiliated Hospital of Wenzhou Medical Univesity from Jan.2008 to Dec.2013 into 4 groups:group A1B1,PCOS patients underwent unstimulated IVM protocol,240 cycles; group A1B2,PCOS patients underwent IVM converted from conventional stimulated IVF protocol,153 cycles; group A2B1,non-PCOS patients underwent unstimutlated IVM protocol,103 cycles; group A2B2,non-PCOS patient underwent IVM converted from conventional stimulated IVF protocol,95 cycles.Multiple linear regression method and binary logistic regression method were used to assess the influence of PCOS and protocols for IVM on laboratory and clinical outcomes.Results The mean number of oocytes retrieved was positively related with PCOS [partial regression coefficient (B)=3.37,P＜0.01].The maturation rate of oocytes was positively related with hCG-prime prior to oocyte aspiration (B=0.05,P=0.010).High-quality embryo rate was positively related with PCOS and IVM converted from IVF (B=0.08,P=0.010; B=0.09,P=0.001),as well as implantation rate related with them (B=0.07,P=0.010; B=0.10,P＜0.01).PCOS and IVM converted from IVF improved hCG positive (hCG＞10 U/L) rate (OR=1.636,95％CI:1.113-2.204,P＜0.05; OR=1.861,95％CI:1.307-2.649,P＜0.05) and the clinical pregnancy rate (OR=1.507,95％CI:1.041-2.240,P＜0.05; OR=1.881,95％CI:1.312-2.696,P＜0.05).IVM converted from IVF protocol decreased the spontaneous abortion rate (OR=0.490,95％CI:0.245-0.978,P＜0.05).Multiple gestation rate and ectopic pregnancy rate were not affected by PCOS condition and protocol used (P＞0.05).Conclusions PCOS and IVM converted from IVF protocol improved the high-quality embryo rate,implantation rate,hCG positive rate and clinical pregnancy rate.IVM converted from IVF protocol reduced the spontaneous abortion rate.PCOS patients may be more suitable for the IVM treatment.No matter PCOS or non-PCOS patients,IVM converted from IVF protocol had better pregnancy outcome than that of unstimulated cycle.

Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L⁻¹ NaAsO₂ model group (NaAsO₂), 50 mg·L⁻¹ NaAsO₂+10 mg·kg⁻¹ GBE intervene group (NaAsO₂+GBE), and 10 mg·kg⁻¹ GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L⁻¹ NaAsO₂, or given intraperitoneal injection of normal saline containing 10 mg·kg⁻¹ GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L⁻¹ NaAsO₂ group (NaAsO₂), 8 μmol·L⁻¹ NaAsO₂ + 200 mg·L⁻¹ GBE intervene group (NaAsO₂+GBE), and 200 mg·L⁻¹ GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO₂ group exhibited an elevated blood glucose compared to the control group, and the NaAsO₂+GBE group showed a decreased blood glucose compared to the NaAsO₂ group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO₂ group and NaAsO₂+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO₂ groups compared to the control groups, which was alleviated in the NaAsO₂+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO₂+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.