Menstrual abnormalities effects on clinical features and in vitro fertilization pregnancy outcomes in women with polycystic ovarian syndrome.

BACKGROUND: The diagnostic criteria and phenotypes in polycystic ovary syndrome are heterogeneous. Currently, it is unclear how to assess a patient's prognosis based on the onset time of menstruation disturbance. Evidence on this topic is scarce and has mainly focused on menstrual patterns. OBJECTIVE: This study aimed to assess the association between the onset time of menstrual disturbance and clinical features and in vitro fertilization pregnancy outcomes in patients with polycystic ovary syndrome. STUDY DESIGN: Our study was a secondary analysis of data collected as part of a randomized controlled trial conducted to compare live birth rates between fresh embryo transfer and frozen embryo transfer in 1508 individuals with polycystic ovary syndrome. Here, 1500 participants were classified into 2 groups according to the onset time of menstrual disturbance: immediately after menarche (early group) and after at least 1 year of regular menstruation (late group). We compared the prepregnancy clinical features, variables of ovarian stimulation, pregnancy outcomes after the initial cycle of embryo transfer, and perinatal and neonatal complications in the 2 groups. RESULTS: Compared with the late group, the early group had more antral follicles (32.00 [range, 27.25-39.50] vs 28.00 [range, 24.00-36.00]; P<.001), an elevated level of antimüllerian hormone (7.02 ng/mL [range, 3.60-11.47] vs 5.66 ng/mL [range, 3.65-8.92]; P=.024), a higher level of baseline luteinizing hormone (10.01±5.93 vs 8.51±5.53 IU/l; P<.001) and luteinizing hormone-to-follicle-stimulating hormone ratio (1.51 [range, 1.00-2.32] vs 1.45 [range, 0.92-2.13]; P<.001), lower levels of fasting glucose (5.47 mmol/L [range, 5.11-5.73] vs 5.50 mmol/L [range, 5.17-5.76]; P<.001), and insulin at 2 hours after 75-g oral glucose tolerance test (56.85 µU/mL [range, 34.63-94.54] vs 59.82 µU/mL [range, 33.56-94.67]; P=.027), a higher level of high-density lipoprotein (1.26 mmol/L [range, 1.04-1.37] vs 1.21 mmol/L [range, 1.07-1.45]; P=.006). During in vitro fertilization, the early group had a higher level of peak estradiol (4596.50 pg/mL [range, 2639.25-6321.00] vs 3954.00 pg/mL [range, 2378.75-6113.50]; P=.013), and luteinizing hormone (2.52 IU/L [range, 1.40-4.21] vs 1.93 IU/L [range, 0.91-3.32]; P=.010) on the day of human chorionic gonadotropin trigger. There was no statistically significant difference observed in the number of oocytes and embryos, the rates of pregnancy and live birth, and the risks of obstetrical and neonatal between the 2 groups. CONCLUSION: An early onset of menstrual disturbance in patients with polycystic ovary syndrome may be associated with slightly more severe reproductive features and slightly milder metabolic features. Nonetheless, the outcomes of in vitro fertilization and the initial cycle of embryo transfer were comparable between the 2 groups.

The difference in early trimester fetal growth between singletons after frozen embryo transfer and fresh embryo transfer.

BACKGROUND: Frozen embryo transfer resulted in a higher birthweight and an increased risk of macrosomia than fresh embryo transfer. However, the mechanism was still unclear. When the impact of frozen embryo transfer on fetal growth began was unknown. Crown-rump length at 11-13 weeks had been regarded as a good indicator of fetal growth in the first trimester and had been used for gestational age calculation in women with uncertain last menstrual periods. OBJECTIVE: To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, then fresh embryo transfer. The secondary objective was to investigate the potential correlation between crown-rump length and birthweight. STUDY DESIGN: This was a retrospective cohort study conducted at the Reproductive Medical Center of Shandong University. A total of 4949 patients who obtained singleton pregnancy after frozen embryo transfer and 1793 patients who got singleton pregnancy after fresh embryo transfer between January 1, 2017 and December 31, 2022 were included. The primary outcome was the crown-rump length measured via ultrasound at 11-13 weeks gestation. The secondary outcomes were perinatal outcomes, including birthweight and the risk of large for gestational age, small for gestational age, macrosomia, low birthweight, and premature delivery. Multivariable linear regression models were used to adjust for potential confounders of crown-rump length. RESULTS: A total of 6742 live singleton births after frozen embryo transfer or fresh embryo transfer were included in this study. In the univariable analysis, the frozen embryo transfer group had a larger crown-rump length (5.75±0.53 cm vs 5.57±0.48 cm, P<.001) and an increased risk of larger-than-expected crown-rump length (13.5% vs11.2%, P=.013) than the fresh embryo transfer group. After adjusting for confounders in multivariable linear regression models, frozen embryo transfer was still associated with a larger crown-rump length (regression coefficient, 3.809 [95% confidence intervals, 3.621-3.997], P<.001). When subgrouped by fetal gender, the crown-rump length of the frozen embryo transfer group was larger than the fresh embryo transfer group in both male and female fetuses. In addition, the crown-rump length was consistently larger in the frozen embryo transfer group than the fresh embryo transfer group in subgroups of the peak estradiol levels. The comparisons among different crown-rump length groups showed that smaller-than-expected crown-rump length was associated with increased risks of small for gestational age (6.3% vs 3.0%, P<.001) and preterm delivery (9.6% vs 6.7%, P=.004) than normal crown-rump length. CONCLUSION: Frozen embryo transfer was associated with a larger crown-rump length than fresh embryo transfer, suggesting that the effect of frozen embryo transfer on fetal growth may begin in the early trimester. Suboptimal fetal growth in the first trimester may be associated with low birthweight and premature delivery.

Interpregnancy Interval After Clinical Pregnancy Loss and Outcomes of the Next Frozen Embryo Transfer.

Importance: The optimal interpregnancy interval (IPI) after a clinical pregnancy loss (CPL) remains controversial. Few studies have addressed the role of the IPI after a preceding CPL during in vitro fertilization (IVF) treatment. Objective: To evaluate the association between different IPI lengths after a preceding CPL and pregnancy outcomes of the next frozen embryo transfer (FET). Design, Setting, and Participants: This retrospective cohort study was conducted using data from the Center for Reproductive Medicine of Shandong University in China. The study included women who underwent frozen-thawed blastocyst transfer between July 1, 2017, and June 30, 2022, within 1 year after a preceding CPL during IVF treatment. Follow-up for pregnancy outcomes was completed for all participants on March 31, 2023. Data analysis was performed from April to May 2023. Exposures: Interpregnancy interval length was classified as less than 3 months, 3 to less than 6 months, or 6 to 12 months. Main Outcomes and Measures: Outcomes included live birth, conception, clinical pregnancy, pregnancy loss, preterm birth, small or large for gestational age, and low birth weight. Multivariable logistic regression analysis was conducted to evaluate the association between IPI and pregnancy outcomes by adjusted odds ratios (AORs). Results: This study included 2433 women (mean [SD] age, 31.8 [4.6] years) who received IVF treatment. There were 338 women (13.9%) with an IPI of less than 3 months, 1347 (55.4%) with an IPI of 3 to less than 6 months, and 748 (30.7%) with an IPI of 6 to 12 months. The median (IQR) IPI lengths for the 3 groups were 77 (65-85), 128 (109-152), and 234 (202-288) days, respectively. Compared with an IPI of 6 to 12 months, shorter IPIs (<3 and 3 to <6 months) were associated with decreased odds of clinical pregnancy (AOR, 0.70 [95% CI, 0.53-0.92] and 0.79 [0.65-0.95]), live birth (AOR, 0.64 [95% CI, 0.48-0.85] and 0.74 [0.61-0.90]), and healthy live birth (AOR, 0.63 [95% CI, 0.46-0.87] and 0.79 [0.64-0.98]). Compared with women with an IPI of 6 to 12 months, women with shorter IPIs (<3 and 3 to <6 months) had a higher risk of total pregnancy loss (AOR, 1.87 [95% CI, 1.31-2.67] and 1.29 [1.00-1.66], respectively). Conclusions and Relevance: The results of this study suggest that delaying the next FET for at least 6 months after a preceding CPL was associated with beneficial pregnancy outcomes, considering that a decreased likelihood of achieving clinical pregnancy and live birth was observed among women with shorter IPIs. Further prospective studies are needed to confirm these findings.

The likelihood of a healthy live birth after frozen embryo transfer with endometrium prepared by natural ovulation regimen vs programmed regimen: a propensity-score matching study.

BACKGROUND: The number of frozen embryo transfer cycles is increasing, but the optimal method of endometrial preparation for frozen embryo transfer remains controversial. Few studies have investigated the healthy live birth outcome after the natural ovulation regimen vs the programmed regimen. OBJECTIVE: This study aimed to explore whether the likelihood of a healthy live birth after frozen embryo transfer differs between the natural ovulation regimen and the programmed regimen. STUDY DESIGN: We conducted a retrospective cohort study including 7824 ovulatory women who underwent the first frozen embryo transfer cycle of single-blastocyst transfer with endometrial preparation by natural ovulation regimen vs programmed regimen, between June 2017 and June 2021. Propensity score matching was used to control for confounding variables in a 1:1 ratio. The primary outcome was healthy live birth, defined as birth of a live, singleton infant born at term, with an appropriate birthweight for gestational age. RESULTS: The natural ovulation regimen resulted in a higher probability of achieving healthy live birth compared with the programmed regimen (35.8% vs 30.6%; P<.0001). In addition, a higher rate of singleton live birth was observed after the natural ovulation regimen relative to the programmed regimen (49.6% vs 45.7%; P=.003). Women with the natural ovulation regimen were also less likely to experience clinical pregnancy loss (16.0% vs 19.7%; P=.005) and hypertensive disorders of pregnancy (3.9% vs 6.0%; P=.004) compared with women with the programmed regimen. Singletons born after the programmed regimen had greater mean birthweight (3441.50±539.97 vs 3394.96±503.87; P=.020) and higher risk of being large for gestational age (23.3% vs 18.7%; P=.003) than those conceived after the natural ovulation regimen. CONCLUSION: The natural ovulation regimen may be superior to the programmed regimen with regard to higher likelihood of healthy live birth and lower risk of pregnancy loss and maternal hypertensive disorders of pregnancy.

The gestational age-specific difference in birthweight between singletons born after fresh and frozen embryo transfer: A cohort study.

INTRODUCTION: Accumulating studies have suggested singletons born after frozen embryo transfer (FET) were higher than those born after fresh embryo transfer (Fre-ET). However, fewer studies had investigated the gestational age-specific between-group difference in birthweight. This study aimed to investigate the gestational week-specific difference in singleton birthweight after FET vs Fre-ET and explore potential factors that impact the difference. MATERIAL AND METHODS: In this retrospective cohort study, a total of 25 863 singletons were included. Multivariable linear regression and logistic regression were used to evaluate the between-group differences in mean birthweight and the incidences of large for gestational age (LGA) and small for gestational age (SGA), respectively. RESULTS: Multivariable regression analyses showed a statistically significant interaction between types of embryo transfer (ie FET vs Fre-ET) and the gestational week on mean birthweight (P < 0.001) and on the risks of large for gestational age (P = 0.001) and small for gestational age (P < 0.001). When stratified by gestational week, the differences in mean birthweight and the risks of LGA and SGA were only observed in singletons born at 37 gestational weeks or later. After adjusting for confounders, full-term but not preterm singletons born after FET had a higher birthweight (3497.58 ± 439.73 g vs 3445.67 ± 450.24 g; adjusted mean difference 58.35 g; 95% confidence interval [CI] 38.72-77.98 g), a higher risk of LGA (24.3% vs 21.1%; adjusted odds ratio [OR] 1.28, 95% CI 1.15-1.42) and a lower risk of SGA (3.1% vs 4.8%; adjusted OR 0.61, 95% CI 0.53-0.70) compared with those born after Fre-ET. CONCLUSIONS: The differences in birthweight between FET and Fre-ET were observed in full-term singletons but not preterm singletons.

The sex-specific difference in singleton birth weight after frozen embryo transfer compared with fresh embryo transfer: a secondary analysis of 3 randomized trials.

OBJECTIVE: To assess whether the between-group difference in singleton birth weight following frozen vs. fresh embryo transfer varied with infant sex. DESIGN: A post hoc exploratory secondary analysis of data from three multicenter randomized trials compared the live birth rates between freeze-only vs. fresh embryo transfer. SETTING: Academic fertility centers. PATIENT(S): A total of 1,886 women who achieved singleton live birth after a frozen or fresh embryo transfer during these trials were included. INTERVENTION(S): Women underwent either a frozen or fresh embryo transfer. MAIN OUTCOME MEASURE(S): Mean birth weight, large for gestational age (LGA), and small for gestational age (SGA). RESULT(S): There was an interaction between the types of embryo transfer and infant sex on the birth weight and on the incidences of LGA and SGA. Among male infants, compared with singletons following fresh embryo transfer, singletons following frozen embryo transfer had higher mean birth weights (3,520.6 ± 526.1 vs. 3,345.1 ± 524.9 g), a higher risk of being LGA (25.2% vs. 15.7%), and a lower risk of being SGA (3.3% vs. 6.1%). However, among the female infants, no statistically significant difference was found in the mean birth weight (3,336.5 ± 514.8 vs. 3,299.5 ± 485.0 g) or the risks of being LGA (18.8% vs. 15.7%) or SGA (5.2% vs. 6.0%) between frozen and fresh embryo transfer. CONCLUSION(S): Male singletons born after frozen embryo transfer were more likely to have a higher birth weight than those born after fresh embryo transfer.

The association of telomere maintenance and TERT expression with susceptibility to human papillomavirus infection in cervical epithelium.

The role of telomerase reverse transcriptase (TERT) induction and telomere maintenance in carcinogenesis including cervical cancer (CC) pathogenesis has been well established. However, it remains unclear whether they affect infection of high-risk human papillomavirus (hrHPV), an initiating event for CC development. Similarly, genetic variants at the TERT locus are shown to be associated with susceptibility to CC, but it is unclear whether these SNPs modify the risk for cervical HPV infection. Here we show that in CC-derived HeLa cells, TERT overexpression inhibits, while its depletion upregulates expression of Syndecan-1 (SDC-1), a key component for HPV entry receptors. The TCGA cohort of CC analyses reveals an inverse correlation between TERT and SDC-1 expression (R = -0.23, P = 0.001). We further recruited 1330 females (520 non-HPV and 810 hrHPV-infected) without CC or high-grade cervical intraepithelial neoplasia to analyze telomeres in cervical epithelial cells and SNPs at rs2736098, rs2736100 and rs2736108, previously identified TERT SNPs for CC risk. Non-infected females exhibited age-related telomere shortening in cervical epithelial cells and their telomeres were significantly longer than those in hrHPV-infected group (1.31 ± 0.62 vs 1.19 ± 0.48, P < 0.001). There were no differences in rs2736098 and rs2736100 genotypes, but non-infected individuals had significantly a higher C-allele frequency (associated with higher TERT expression) while lower T-allele levels at rs2736108 compared with those in the hrHPV group (P = 0.020). Collectively, appropriate telomere maintenance and TERT expression in normal cervical cells may prevent CC by modulating hrHPV infection predisposition, although they are required for CC development and progression.

WWOX promotes apoptosis and inhibits autophagy in paclitaxel­treated ovarian carcinoma cells.

Although paclitaxel (PTX) is a first­line chemotherapeutic agent for the treatment of epithelial ovarian cancer (EOC), its clinical use is restricted by chemoresistance. Autophagy is believed to promote drug resistance, and WW domain­containing oxidoreductase (WWOX) has been predicted to serve an essential role in apoptosis induction and to suppress autophagy in various tumor cell types. In the present study, the role of WWOX was demonstrated using PTX­treated EOC cells. Cell viability and apoptosis were detected using Cell Counting Kit­8, morphological and flow cytometric analyses. WWOX and phosphorylated (p)­WWOX were highly expressed in PTX­treated sensitive EOC cells (A2780), which was accompanied by activation of the apoptosis­related proteins caspase­3 and poly (ADP­ribose) polymerase (PARP). Conversely, PTX­resistant EOC cells (A2780/T) were characterized by reduced WWOX expression and constant phosphorylation levels, as well as undetectable levels of activated caspase­3 and PARP when cells were treated with PTX. The altered expression of WWOX between the two cell types was further validated by reverse transcription­-quantitative PCR. The apoptosis­inducing role of WWOX was also confirmed by flow cytometry after WWOX overexpression was induced in PTX­treated A2780 cells. These findings indicated that WWOX activation may inhibit chemoresistance and trigger cancer cell death. The upregulated expression levels of the autophagy­related protein 12­5 complex, Beclin­1 and LC3, as well as the downregulation of P62, were also detected following PTX treatment, suggesting that PTX induced autophagic flux in both types of EOC cells. This conclusion was further supported by visualizing the accumulation of autophagosome and autolysosome vesicles, using confocal microscopy and transmission electron microscopy. PTX was also shown to inhibit mTOR signaling, indicated by a decreased level of p­mTOR and increased expression of eukaryotic translation initiation factor 4E­binding protein 1. Finally, the interaction between WWOX, mTOR and autophagy was investigated via WWOX transfection experimentation, and indicated that WWOX activated mTOR whilst inhibiting autophagy. These data indicated that WWOX may serve a critical role in PTX­induced apoptosis and could suppress autophagy by downregulating essential autophagic effectors in EOC cells via mTOR signaling.

Live birth after a freeze-only strategy versus fresh embryo transfer in three randomized trials considering progesterone concentration.

RESEARCH QUESTION: Is there a difference in live birth rate between a freeze-only strategy and fresh embryo transfer, and what is the effect of varying progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration? DESIGN: A secondary analysis of data from three randomized trials comparing the live birth rate after elective frozen versus fresh embryo transfer, which respectively enrolled 1508 women with polycystic ovary syndrome, 2157 ovulatory women who underwent cleavage-stage embryo transfer and 1650 ovulatory women who underwent single blastocyst transfer. Women were randomly assigned to the frozen or fresh embryo transfer group in the original trials. The primary outcome was live birth rate after the initial embryo transfer. RESULTS: The live birth rate after a freeze-only strategy was consistently higher than fresh embryo transfer at any progesterone concentration on the day of HCG administration. Nonetheless, the between-group difference in live birth rate after frozen versus fresh embryo transfer was greater in women with progesterone concentrations ≥1.14 ng/ml (52.7% versus 37.3%, odds ratio (OR) 1.88, 95% confidence interval (CI) 1.55-2.27, P = 7.89 â€¯×  10-11) than in women with progesterone concentrations <1.14 ng/ml (53.3% versus 48.1%, OR 1.23, 95% CI 1.08-1.41, P = 0.002). In women with progesterone concentration ≥1.14 ng/ml, frozen embryo transfer also resulted in higher rates of conception and clinical pregnancy than fresh embryo transfer. CONCLUSION: In women with normal or high ovarian response, a freeze-only strategy resulted in a higher live birth rate than fresh embryo transfer, irrespective of progesterone concentration. Moreover, women with progesterone concentration ≥1.14 ng/ml may benefit more from a freeze-only strategy.

Effect of preoperative gabapentin after transurethral prostate resection under general anesthesia. A randomized double-blind, placebo-controlled trial.

OBJECTIVES: To investigate whether preoperative oral gabapentin could reduce postoperative pain, analgesic consumption and the occurrence of catheter-related bladder discomfort (CRBD). Methods: In this study, participants randomly received either 600 mg gabapentin or placebo orally 2 h prior to transurethral prostate resection. Visual analogue scale and Ramsay sedation scale was utilized to assess pain intensity and sedation status after surgery. Intravenous 1.5 mg.kg-1 tramadol was used for postoperative analgesia. Pain intensity, sedation status, CRBD, tramadol consumption, side effects and the overall satisfaction degree were assessed and recorded for 48 h after tracheal extubation.  Results: Ninety participants given gabapentin and 91 participants given placebo completed the study. Lower visual analogue scale scores, less tramadol consumption, longer time to the first analgesic requirement, lower incidence of CRBD and nausea and higher satisfaction degree were detected in the patients receiving gabapentin compared with the patients receiving placebo.  Conclusion: Preoperative oral gabapentin reduced postoperative visual analogue scale scores, tramadol consumption and the occurrence rate of CRBD and nausea, and consequently, increased the degree of patients' satisfaction after transurethral prostate resection.

Risk factors associated with pre-eclampsia in pregnancies conceived by ART.

RESEARCH QUESTION: What are the factors associated with the increased incidence of pre-eclampsia in pregnancies conceived through IVF using autologous oocytes? DESIGN: A nested case-control study from the combined cohort of three multicentre randomized trials comparing fresh to frozen embryo transfer, including women who achieved clinical pregnancy after the first embryo transfer. Multivariable logistic regression was used to assess the effect of baseline characteristics, ovarian response parameters, type of fertilization, type of embryo transfer, and number of gestational sacs on the risk of pre-eclampsia. RESULTS: There were 2965 clinical pregnancies and 90 women were diagnosed with pre-eclampsia. Twin gestations (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.50-3.66), mean arterial pressure (OR 1.04, 95% CI 1.01-1.07), frozen embryo transfer (OR 2.06, 95% CI 1.27-3.35), body mass index (BMI) (OR 1.10, 95% CI 1.02-1.18), progesterone level on the day of human chorionic gonadotrophin trigger (OR 1.53, 95% CI 1.07-2.20), and the total dose of gonadotrophin (OR 0.999, 95% CI 0.999-1.000, P = 0.037) were associated with the risk of pre-eclampsia. When the analysis was confined to women who underwent frozen embryo transfer, twin gestations (OR 2.44, 95% CI 1.43-4.18), BMI (OR 1.13, 95% CI 1.03-1.23) and the total dose of gonadotrophin (OR 0.999, 95% CI 0.999-1.000, P = 0.014) were still related to the risk of pre-eclampsia. The embryo stage at transfer was not included in the final models. CONCLUSIONS: Frozen embryo transfer was an independent risk factor of pre-eclampsia in assisted reproductive technology. The high ovarian response may also increase the risk of pre-eclampsia. The embryo stage at transfer was not related to the risk of pre-eclampsia.

The Effect of Supraphysiological Estradiol on Pregnancy Outcomes Differs Between Women With PCOS and Ovulatory Women.

Context: Supraphysiological estradiol exposure after ovarian stimulation may disrupt embryo implantation after fresh embryo transfer. Women with polycystic ovary syndrome (PCOS), who usually overrespond to ovarian stimulation, have a better live birth rate after frozen embryo transfer (FET) than after fresh embryo transfer; however, ovulatory women do not. Objective: To evaluate whether the discrepancy in live birth rate after fresh embryo transfer vs FET between these two populations is due to the variation in ovarian response (i.e., peak estradiol level or oocyte number). Design, Setting, Patients, Intervention(s), and Main Outcome Measure(s): This was a secondary analysis of data from two multicenter randomized trials with similar study designs. A total of 1508 women with PCOS and 2157 ovulatory women were randomly assigned to undergo fresh or FET. The primary outcome was live birth. Results: Compared with fresh embryo transfer, FET resulted in a higher live birth rate (51.9% vs 40.7%; OR, 1.57; 95% CI, 1.22 to 2.03) in PCOS women with peak estradiol level >3000pg/mL but not in those with estradiol level ≤3000 pg/mL. In women with PCOS who have ≥16 oocytes, FET yielded a higher live birth rate (54.8% vs 42.1%; OR, 1.67; 95% CI, 1.20 to 2.31), but this was not seen in those with <16 oocytes. In ovulatory women, pregnancy outcomes were similar after fresh embryo transfer and FET in all subgroups. Conclusions: Supraphysiological estradiol after ovarian stimulation may adversely affect pregnancy outcomes in women with PCOS but not in ovulatory women.

MicroRNA-326 suppresses the proliferation, migration and invasion of cervical cancer cells by targeting ELK1.

Although microRNAs (miRNAs or miRs) are able to function as oncogenes or tumor suppressors, the role of miR-326 in regulating human cervical cancer cells remains unclear. In the present study, the expression of miR-326 was identified to be downregulated in cervical cancer cell lines and primary tumor samples, and the overexpression of miR-326 decreased cell proliferation, migration and invasion in cervical cell lines. Bioinformatics prediction and experimental validation results revealed that the function of miR-326 was achieved by targeting and repressing ETS domain-containing protein Elk-1 (ELK1) expression. ELK1 was targeted directly by miR-326, which was downregulated in human cervical cancer tissues compared with that in adjacent normal tissues. The results of the present study suggest that miR-326, a potential tumor suppressor, may be used in the treatment of cervical cancer.

Involvement of enhancer of zeste homolog 2 in cisplatin-resistance in ovarian cancer cells by interacting with several genes.

In the present study, gene expression profiles of cisplatin-sensitive ovarian cancer (OC) cells were compared with those of cisplatin-resistant OC cells to identify key genes and pathways contributing to cisplatin resistance in ovarian cancer cells. The GSE15372 gene expression data set was downloaded from Gene Expression Omnibus, and included five biological replicates of cisplatin-sensitive OC cells and five biological replicates of cisplatin-resistant OC cells. Differentially expressed genes (DEGs) were screened using the limma package in R, based on the cut-off values of P<0.05 and |log2 (fold change)|>1. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology enrichment analysis were performed on the DEGs using the Database for Annotation, Visualization and Integration Discovery. The protein-protein interaction (PPI) network was constructed for the DEGs using STRING, and sub-networks were analyzed by Clustering with Overlapping Neighborhood Expansion. A total of 556 DEGs were identified in the cisplatin-sensitive OC cells, of which 246 were upregulated and 310 were downregulated. Functional enrichment analysis revealed metabolism-associated pathways, DNA replication and cell cycle were significantly enriched in the downregulated genes, while cell growth and differentiation, response to stimulus, and apoptosis were significantly enriched in the upregulated genes. A PPI network, including 342 nodes was constructed for the DEGs and four subnetworks were extracted from the entire network. A total of 34 DEGs interacting with enhancer of zeste homolog 2 (EZH2) were identified, which were associated with DNA replication, pyrimidine metabolism and cell cycle. In conclusion, a number of key genes and pathways associated with the cisplatin-resistance of OC were revealed, particularly EZH2. These findings assist in the development of therapy for OC.

Clinicopathological risk factors for recurrence after neoadjuvant chemotherapy and radical hysterectomy in cervical cancer.

BACKGROUND: Cervical cancer is one of the common gynecological malignancies with a high recurrence rate after surgery. This study aimed to analyze the clinicopathological risk factors for recurrence after the surgical treatment of cervical cancer and provide the basis for the prevention of recurrence and an improvement of prognosis. METHODS: A total of 424 cervical cancer cases between 1 January 1998 and 31 December 2011 undergoing surgical treatment were studied retrospectively, of which 23 cases had recurrences. Relevant recurrence risk factors were evaluated by univariate and multivariate analyses between recurrence group and non-recurrence group. RESULTS: Using univariate analysis, tumor differentiation, clinical stage, pelvic lymph node metastasis, postoperative radiotherapy and postoperative chemotherapy were related to recurrence of cervical cancer. Multivariate COX model analysis revealed that pelvic lymph node metastasis and postoperative chemotherapy had an impact on recurrence rate. Moderately and highly differentiated tumor, advanced clinical stage, and positive pelvic lymph nodes indicated a high recurrence rate of cervical cancer. Postoperative chemotherapy and radiotherapy can effectively reduce the recurrence rate. CONCLUSIONS: In conclusion, cervical lymph node metastasis and postoperative chemotherapy are two independent factors for recurrence of cervical cancer after radical surgery.

[Differential anti-tumor effects for various regimens of endostar plus cisplatin in ovarian cancer].

OBJECTIVE: To find the time window of normalization of tumor vasculature by endostar in tumor-bearing mice with ovarian cancer. METHODS: The nude murine model of ovarian cancer was established. The vasculature markers α-SMA (alpha-smooth muscle actin) and collagen IV covered tumor vessels and hypoxic zone following the treatment of endostar were monitored. According to the changes of microvascular morphology and tumor hypoxia zone, the time window was identified. Furthermore the treatment protocols of scheduling dosing of cisplatin plus endostar at different time points were designed. After treatment tumor volume, the parameters of microvascular density (MVD) and PCNA (proliferating cell nuclear antigen) were monitored to evaluate the effects of different protocols. RESULTS: At Days 4 and 6 post-treatment, more α-SMA and collagen IV covered vessels could be observed. The amount of microvasculature expressed α-SMA on days 4 compared with control was (15.3 ± 5.2) vs (4.3 ± 2.1)/mm(2) (P < 0.01); at Day 6, the result was (16.4 ± 4.6) vs (6.6 ± 2.4)/mm(2)(P < 0.01). The expression of collagen IV had a similar change. And the numbers of microvasculature expressing collagen IV was (14.7 ± 4.3) vs (6.7 ± 5.1)/mm(2) at Days 4 and 6 (P < 0.01); (18.4 ± 5.5) vs (7.1 ± 1.7)/mm(2) (P < 0.01). The expression of HIF-1α decreased in hypoxic area. In the rhES + DDP (d4-6) group, the value of microvessel density (MVD) decreased and the expression of PCNA significantly decreased versus other groups. CONCLUSION: Endostar may normalize the tumor vasculature. And the time window is found at Days 4-6 post-treatment. During the time of vascular normalization, a combination therapy of endostar plus cisplatin has optimal efficacies.

Neovagina constructed with the peritoneum of the anterior abdominal wall.

OBJECTIVE: To describe the successful construction of a neovagina with the peritoneum from the anterior abdominal wall for six hypermicrosomic patients diagnosed with Rokitansky syndrome. MATERIAL & METHODS: A neovagina was created using peritoneum from the anterior abdominal wall. RESULTS: The mean depth of the neovaginas was 11 cm and the diameter was 2.5 cm. The mucosa of the neovaginas was pinkish and had a moist surface. No intraoperative or postoperative complications were observed. The patients enjoyed sexual activity after the operation. CONCLUSIONS: The application of the peritoneum from the anterior abdominal wall for the hypermicrosomic patient diagnosed with Rokitansky syndrome has the advantage of providing sufficient length for the creation of a neovagina.

Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines.

BACKGROUND: To observe mRNA expression of tumor-specific antigen MAGE, BAGE and GAGE in epithelial ovarian cancer tissues and cell lines, to explore the relationship between gene expression and diagnosis, treatment and prognosis of ovarian cancer, and to evaluate the feasibility of their gene products as markers, and an immunotherapy target for ovarian cancer. METHODS: mRNA expression of MAGE-1, MAGE-3, GAGE-1/2 and BAGE were determined by reverse transcription polymerase chain reaction (RT-PCR) in 14 cases of normal ovarian tissue, 20 cases of ovarian benign tumor specimens, 41 cases of ovarian cancer specimens, and ovarian cancer cell lines SKOV3, A2780, and COC1. RESULTS: MAGE, GAGE and BAGE genes were not expressed in normal ovarian tissue. In benign tumors, only the MAGE gene was expressed; the expression rate of this gene in benign tumors was 15% (3/20). In ovarian cancer tissues, MAGE-1 and MAGE-3 was highly expressed, with expression rates of 53.7% (22/41) and 36.6% (15/41), while GAGE-1/2 and BAGE had relatively low expression, with rates of 26.8% (11/41) and 14.6% (6/41). In metastatic lesions of ovarian cancer, only MAGE-1 and BAGE were expressed, with expression rates of 28.6% (2/7) and 14.3% (1/7). The positive expression rates of MAGE-1 and MAGE-3 in serous cystadenocarcinoma were significantly higher than that in other types of ovarian cancer (P < 0.05). Gene expression rate was not correlated with menopause or lymph node metastasis. Positive expression of MAGE-1 and MAGE-3 was positively correlated with tumor differentiation and the clinical stage of the ovarian cancer. In addition, the positive expression rate of BAGE was significantly higher in ovarian cancer patients with ascites (P < 0.05). The mRNA expression profiles of MAGE, GAGE and BAGE in ovarian carcinoma cell lines SKOV3, A2780 and COC1 varied, but there was at least one gene expressed in each cell line. CONCLUSION: Tumor-specific antigen MAGE, BAGE and GAGE may play a role in the occurrence and development of ovarian cancer. These genes can be used as one of the important indicators for early diagnosis, efficacy evaluation and prognostic determination of ovarian cancer.

[The effects of anti-inflammatory and anti-asthmatic agents on CD34+ hematopoietic cells in bone marrow of asthmatic mice].

OBJECTIVE: To observe the effects of glucocorticoids and cysteinyl leukotrienes 1 receptor antagonist on CD(34)(+) hematopoietic cells, and to study the rationality of a bone marrow-targeting anti-inflammatory strategy. METHODS: Twenty-four BALB/c mice were sensitized and challenged by 1% ovalbumin (OVA) to establish the asthmatic model. Asthmatic mice were challenged by 1% OVA and divided into 4 groups: fed by sterile saline (group A), prednisone (group B), montelukast (group C) and prednisone plus montelukast (group D) respectively for two consecutive weeks. The mice were killed at 24 h after the last challenge, then bronchoalveolar lavage fluid (BALF), peripheral blood and bone marrow were prepared. Eosinophils in peripheral blood and BALF, nucleate cells in BALF, peripheral blood and bone marrow were counted. The percentage of CD(34)(+) cells, CD(4)(+), CD(8)(+) T lymphocyte to nucleate cells in peripheral blood and bone marrow were counted by flow cytometry. Immunocytochemistry and in situ hybridization were employed to detect the hematopoietic cells expression of CD(34)(+) and IL-5Ralpha mRNA in bone marrow (CD(34)(+) IL-5Ralpha mRNA(+) cells). RESULTS: The number of EOS in BALF and peripheral blood and the number of CD(34)(+) cells in peripheral blood and bone marrow in group A were [(18.3 +/- 1.3) x 10(5)/L], [(2.5 +/- 0.4) x 10(8)/L], [(9.6 +/- 5.1) x 10(7)/L] and [(7.7 +/- 3.2) x 10(7)/femur] respectively, compared with the corresponding indices in group B [(4.6 +/- 1.7) x 10(5)/L, (1.5 +/- 0.3) x 10(8)/L, (3.9 +/- 2.1) x 10(7)/L, (3.3 +/- 1.8) x 10(7)/femur] and group D [(3.7 +/- 1.4) x 10(5)/L, (1.7 +/- 0.3) x 10(8)/L, (4.1 +/- 1.8) x 10(7)/L, (2.2 +/- 0.7) x 10(7)/femur]; the differences all were significant (all P < 0.01). The number of bone marrow CD(34)(+) IL-5Ralpha mRNA(+) in group B and D were (23 +/- 7)% and (21 +/- 4)%, as compared with the corresponding index in group A [(37 +/- 4)%], the differences were significant (P < 0.01); the number of eosinophils in BALF in group C was (12.2 +/- 1.1) x 10(5)/L, as compared with the corresponding index in group A [(18.3 +/- 1.3) x 10(5)/L], the difference was significant (P < 0.05). CONCLUSIONS: Prednisone probably inhibits the proliferation, differentiation and emigration of CD(34)(+) cells in the bone marrow of asthmatic mice, and inhibits eosinophilopoiesis in bone marrow, eosinophil migration into peripheral blood and recruitment to the airways. Montelukast may suppress eosinophil infiltrating into lungs of asthmatic mice, but it does not inhibit the proliferation and emigration of CD(34)(+) cells and does not show apparent synergistic effect with prednisone.

[An experimental study of gastric pacing on postsurgical gastric dynamic dysfunction].

OBJECTIVE: To probe the feasibility and curative effect of gastric pacing on postsurgical gastric dynamic dysfunction. METHODS: Thirty-two rabbits were divided into four groups. The gastric dynamic indices of applying gastric pacing to the experimental animal model of acute post-vagotomy gastroparesis were compared with those of the groups treated with erythromycin (1 mg/kg). RESULTS: The measurements of "gastroduodenal pressure at different sites" of the gastric pacing group and erythromycin group were higher than those of the before pacing group respectively (P < 0.001). The gastric pressure of the gastric pacing group was higher than that of the erythromycin group (P < 0.001). No significant difference in the duodenal pressure was observed between the above two groups (P > 0.05). The measurements of pressure at different sites (gastric fundus; gastric corpus; gastric antrum) after stopping pacing were higher than those of the erythromycin group, respectively (P < 0.01, P < 0.05, P < 0.05). The "pressure gradient between gastric antrum and duodenum" of the gastric pacing group was higher than that of the erythromycin group (P < 0.01). The gastric emptying rate of the gastric pacing group (64.41% +/- 6.66%) was significantly higher than that of the erythromycin group (53.73% +/- 7.09%) (P < 0.01). CONCLUSION: Applying higher frequency gastric pacing can markedly enhance the gastric pressure, the pressure gradient between gastric antrum and duodenum, and the gastric emptying rate.