Plasma visfatin and apelin levels in adolescents with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that usually begins during adolescence. Patients may have severe metabolic disorders. OBJECTIVE: To investigate the levels of visfatin and apelin in adolescent girls with PCOS and to explore the importance of visfatin and apelin in glucose and lipid metabolism. METHODS: A total of 88 girls (aged 12-20 years) were prospectively and consecutively recruited during two years for the PCOS group (n = 44) and the control group (n = 44). Serum visfatin, apelin and other metabolic parameters were measured. Receiver operator characteristics (ROC) curve analysis was performed to reveal the diagnostic potential. RESULTS: Visfatin, apelin and indicators of glucose and lipid-metabolism were not different for PCOS patients compared to control. However, insulin resistance (IR) in the PCOS-group was more frequent (p < 0.05). Visfatin in non-IR patients was higher than in IR-patients in the PCOS-group (p < 0.05). However, there was no difference in apelin levels between IR and non-IR patients in the PCOS-group (p > 0.05). ROC-curve analyses demonstrated that the optimal value of visfatin for predicting IR in PCOS-patients was 7.14 ng/mL, with 78.1% sensitivity and 68.7% specificity. In the PCOS-group, visfatin was positively correlated with high density lipoprotein cholesterol (HDL-C), and negatively correlated with HOMA-IR, apolipoprotein B (Apo-B), cholesterol (CHO), low density lipoprotein cholesterol (LDL-C) and CHO/HDL-C ratio (p < 0.05). Apelin had no correlation with all indices (p > 0.05). CONCLUSIONS: Higher visfatin levels may prevent IR in adolescent PCOS patients, showing a positive predictive value for IR and also reflecting a beneficial effect on lipids. It is a possible protective factor at certain stages of metabolic syndrome.

Association between the occurrence of adenomyosis and the clinical outcomes of vaginal repair of cesarean section scar defects: an observational study.

BACKGROUND: To examine the correlation between the occurrence of adenomyosis and the outcome of vaginal repair of cesarean section scar defects (CSDs). METHODS: A total of 278 women with CSD were enrolled in this retrospective observational cohort study at the Shanghai First Maternity & Infant Hospital between January 2013 and August 2017. Patients were divided into two groups according to preoperative magnetic resonance imaging (MRI) findings: the adenomyosis group and the non-adenomyosis group. They all underwent vaginal excision and suturing of CSDs and were required to undergo examinations 3 and 6 months after surgery. Preoperative and postoperative clinical information was collected. Optimal healing was defined as a duration of menstruation of no more than 7 days and a thickness of the residual myometrium (TRM) of no less than 5.8 mm after vaginal repair. RESULTS: Before vaginal repair, for patients in the adenomyosis group, the mean duration of menstruation was longer and TRM was significantly thinner than those in patients in the non-adenomyosis group (p < 0.05). The TRM and duration of menstruation 3 and 6 months after surgery were significantly improved in both groups (p < 0.05). There were more patients with optimal healing in the non-adenomyosis group than in the adenomyosis group (44.7% vs. 30.0%; p < 0.05). Furthermore, 59.3% (32/54) of the women tried to conceive after vaginal repair. The pregnancy rates of women with and without adenomyosis were 66.7% (8/12) and 61.9% (26/42), respectively. The duration of menstruation decreased significantly from 13.4 ± 3.3 days before vaginal repair to 7.6 ± 2.3 days after vaginal repair in 25 patients (p < 0.001). The TRM increased significantly from 2.3 ± 0.8 mm before vaginal repair to 7.6 ± 2.9 mm after vaginal repair (p < 0.001). CONCLUSIONS: Vaginal repair reduced postmenstrual spotting and may have improved fertility in patients with CSDs. Patients with adenomyosis are more likely to have suboptimal menstruation and suboptimal healing of CSDs. Adenomyosis might be an adverse factor in the repair of uterine incisions.

Effect of orlistat during individualized comprehensive life-style intervention on visceral fat in overweight or obese PCOS patients.

ObjectiveTo investigate the effect of orlistat combined with drospirenone/ethinylestradiol tablets (DRSP/EE) on the visceral fat area (VFA) compared to DRSP/EE-alone in overweight or obese patients with polycystic ovary syndrome (PCOS).Methods90 PCOS patients [body mass index (BMI) ≥24kg/m2] were recruited for a prospective, open-label, 1:2 paired 3-monthly study. All were included during the per-protocol defined recruitment time and numbered according to the entry-order: group-1: No.1-60, orlistat plus DRSP/EE; group-2: No.61-90, DRSP/EE-alone. Both groups received the same comprehensive intervention in terms of individualized, standardized management and lifestyle monitoring such as diet and exercise. Primary study-endpoint was VFA, secondary endpoints were anthropometric indices, sex hormones and glucolipid metabolism. Within- and between-group analyses were performed.ResultsVFA [cm2] in group-1 after treatment decreased significantly (p = 0.001), and the between-group comparison was highly significant (p = 0.001). Body weight, hip circumference (HC), BMI, body fat (BF), free testosterone (FT) and low-density lipoprotein-cholesterol (LDL-C) significantly decreased in both groups (within-group analysis); the decrease in group-1 was significantly greater than in group-2 (p < 0.05). Systolic and diastolic blood pressure (SBP/DBP) and fasting plasma glucose (FPG) in group-1 were significantly decreased, significantly more in group-1 than in group-2 (p < 0.05).ConclusionThis study is the first to investigate the effect of orlistat combined with DRSP/EE in overweight or obese PCOS patients compared with using DRSP/EE-alone. Orlistat combined with DRSP/EE was better than using DRSP/EE-alone in reducing VFA, body weight, FT, BP and FPG, which provides evidence for the choice of rational drug use in clinical practice.

Is anti-Mullerian hormone a useful biomarker in the diagnosis of polycystic ovary syndrome in Chinese adolescents?

OBJECTIVE: (1) To investigate anti-Mullerian-hormone (AMH) in adolescents with polycystic ovary syndrome (PCOS) compared to age-matched girls without PCOS; (2) to determine whether AMH is a valuable marker for diagnosing PCOS and to explore the best cutoff value in adolescents; (3) using a multivariate predictive model for the diagnosis of PCOS. METHODS: Ninety girls (aged 10-20 years) recruited during two years for the PCOS-group (n = 45) or control-group (n = 45). PCOS diagnostic criteria according guidelines of the Endocrinology Expert Group, Obstetrics/Gynecology Branch of the Chinese Medical Association. Serum AMH and other sex hormones were measured. Logistic regression analysis to estimate the odds ratio of AMH and other variables for the diagnosis of PCOS. Receiver operator characteristics (ROC) curve analysis was performed to reveal the diagnostic potential. RESULTS: (A) AMH was significantly higher in PCOS patients than in controls (10.21 ± 5.85 ng/ml vs. 4.31 ± 2.84 ng/ml, p < .001). In PCOS-group, total testosterone (TT), free testosterone (FT) and biologically active testosterone (BioT) were significantly higher than in controls (p < .001). (B) Logistic regression suggests that AMH and TT are correlated with the diagnosis of PCOS (p < .05). (C) ROC curve analyses demonstrated that the optimal value of AMH for predicting PCOS was 6.32 ng/mL, with 69.8% sensitivity and 80.5% specificity. Furthermore, AMH combined with TT can provide 83.7% sensitivity and 80.5% specificity for diagnosing PCOS in adolescents. CONCLUSIONS: AMH may be a useful biomarker for the diagnosis of PCOS in Chinese adolescent girls. A cutoff value of 6.32 ng/mL best discriminated between PCOS patients and controls. Besides AMH a multivariate predictive model should include TT.

How much total ovarian tissue can be removed without compromising ovarian function? An animal study.

OBJECTIVE: Removal of ovarian tissue is a new option for fertility preservation for certain cancer patients in China. The aim was to investigate the impact of stepwise removed tissue on hormone levels and follicles in rats. METHODS: Six to ten-week old rats were divided into six groups (% total ovarian tissue): 1 = control (100%), 2 (75%), 3 (50%), 4 (25%), 5 (12.5%), 6 (0%, bilateral ovariectomy). Blood test was carried out fortnightly to assess estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and inhibin B (INHB). Ovaries are obtained from surgical resections and from rats sacrificed after 12 weeks. RESULTS: During 12 weeks, groups 4, 5, and 6 had higher FSH and lower AMH and INHB values compared to control (p< .05), but in group 4 E2 and P was not significantly different from control (p> .05). All ovarian function parameters stopped in groups 5 and 6. Follicle morphology was not significantly different between baseline and 12 weeks after surgery in groups 1-5. CONCLUSIONS: For the first time, we demonstrated that even up to 75% of total ovarian tissue can be removed without impact on E2 and P production in rats, which, if confirmed in women, would mean that hazardous (or possibly contraindicated in cancer patients) hormone therapy is not required to avoid the negative consequences of hormone depletion.

Vaginal repaired cesarean section diverticulum is beneficial in women with two prior cesarean sections.

BACKGROUND: The aim of this study was to evaluate the effect of vaginal repair in patients with cesarean section diverticulum (CSD) who had one or two previous cesarean sections (CSs). METHODS: From January 2012 to December 2014, 248 women with CSD underwent vaginal repair surgery in Shanghai First Maternity and Infant Hospital. These included 193 women with one previous cesarean section and 55 women with two previous cesarean sections. Excision and suture of CSD was performed through a vaginal approach. The duration of menstruation, the length, width and depth of the CSD and thickness of the remaining muscular layer (TRM) were evaluated before and after surgery by transvaginal three-dimensional (3D) color Doppler ultrasound. RESULTS: A total of 221 (89.11%) women were followed-up for more than 3 months, and 168 (67.74%) women were followed-up for more than 6 months. There were significant differences in the average duration of menstruation (7.77 ± 2.05 and 8.02 ± 2.06 days VS 13.99 ± 3.71 days), the average size of CSD (5.54*9.19*5.60 and 5.75*9.04*6.18 mm VS 7.99*12.43*6.62 mm) and the TRM (7.61 ± 2.52 and 7.60 ± 3.00 mm VS 2.51 ± 1.02 mm) after surgery compared with those figures before surgery. The results of this study reveal that vaginal repair could shorten the duration of menstruation and improve anatomical defects (P < 0.05). Moreover, there was no significant difference in the effect of clinical repair between women with one or two previous cesarean sections (P > 0.05). CONCLUSION: In CSD patients, the clinical effectiveness of vaginal repair was equivalent between women with one or two previous cesarean sections.

Simultaneous quantitation of four androgens and 17-hydroxyprogesterone in polycystic ovarian syndrome patients by LC-MS/MS.

BACKGROUND: Due to the low concentration of androgens in women and the limitation of immunoassays, it remains a challenge to accurately determine the levels of serum androgens in polycystic ovary syndrome (PCOS) patients for clinical laboratories. In this report, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantitation of testosterone (T), androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), and 17-hydroxyprogesterone (17-OHP) that are associated with PCOS. METHODS: The serum samples were processed by protein precipitation and solid phase extraction before analysis with the in-house developed LC-MS/MS. The chromatographic separation was achieved with a C18 column, using a linear gradient elution with two mobile phases: 0.02% formic acid in water (phase A) and 0.1% formic acid in methanol (phase B). The separated analytes were detected by positive or negative electrospray ionization mode under multiple reaction monitoring (MRM). RESULTS: The assay for all the five analytes was linear, stable, with imprecision less than 9% and recoveries within ±10%. The lower limits of quantification were 0.05, 0.05, 5, 0.025, and 0.025 ng/mL for T, A4, DHEAS, DHT, and 17-OHP, respectively. In the receiver operating characteristic curve (ROC) analyses with the PCOS (n = 63) and healthy (n = 161) subjects, the AUC of the four-androgen combined was greater than that of any single androgen tested in PCOS diagnosis. CONCLUSIONS: The LC-MS/MS method for the four androgens and 17-OHP showed good performance for clinical implementation. More importantly, simultaneous quantitation of the four androgens provided better diagnostic power for PCOS.

Ovarian tissue cryopreservation: prospective randomized study on thawed ovarian tissue viability to estimate the maximum possible delivery time of tissue samples.

Ovarian tissue cryopreservation is one of the most important methods to protect female fertility, but we just recently established the first central laboratory in China, now building a network with other hospitals. The aim was to estimate the thawed ovarian tissue viability and to explore the feasibility of short-distance transportation. Fifteen samples were obtained from each of 11 patients, i.e. in total 165 samples. One fresh sample was used for follicle counts, 14 punches were cryopreserved, thawed, and randomly divided into seven groups depending on the time after thawing: 0, 20, 40, 60, 80, 100, 120 min. Follicle counts, steroid hormones, and lactate levels were assessed. No significant differences for the three parameters of tissue viability comparing the seven groups were seen. The time can last up to two hours for the delivery of tissue samples from the laboratory to the surgery room. To our knowledge, this question has been tested for the first time systematically within a prospective randomized comparative study.

Vaginal Repair of Cesarean Section Scar Diverticula Diagnosed in Non-pregnant Women.

STUDY OBJECTIVE: Cesarean section scar diverticulum (CSD) lead to many long-term complications. CSD is more prevalent in patients with a retroflexed uterus than in those with an anteflexed uterus. Therefore, we wanted to estimate the association between flexion of the uterus and the outcome of treatment for CSD treated by vaginal repair. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: A total of 241 women with a CSD were enrolled at the Shanghai First Maternity & Infant Hospital between May 2014 and Oct 2016. INTERVENTIONS: Vaginal excision and suture of CSD. MEASUREMENT AND MAIN RESULTS: A high failure rate was reported in remodeling of the scar by other surgeries in women with retroflexed uteri. Clinical information was obtained from medical records. Because intermenstrual bleeding was a presenting symptom of CSD, duration of menstruation was compared between groups. Patients were required to be followed at 1, 3, and 6 months to record their menstruation situation and to measure the CSD. The thickness of the residual myometrium (TRM) in the retroflexion group was much thinner than that in the anteflexion group before treatment (2.5 ± 1.2 mm vs 2.9 ± 1.1 mm, p < .05). There was no statistical difference in pretreatment menstruation duration between groups (p > .05). The duration of menstruation in the anteflexion group was 8.2 ± 2.1 days and 8.5 ± 2.1 days and in the retroflexion group was 7.6 ± 2.0 days and 7.7 ± 3.1 days at 3 and 6 months after surgery, respectively (p < .05). In all 58.6% of patients (140/239) who had a retroflexed uterus, 60.0% (84/140) reached ≤7 days of menstruation at 6 months after surgery (p < .05). Although about 40% patients still had CSD after repair, menstruation duration and TRM were improved significantly (p < .05). CONCLUSION: We propose that vaginal repair can relieve symptoms and improve TRM for CSD patients, especially for those who have a retroflexed uterus. However, 40% of patients still had a defect postoperatively.

Oxidative stress indicators in Chinese women with PCOS and correlation with features of metabolic syndrome and dependency on lipid patterns.

OBJECTIVE: The aim was to investigate oxidative stress indicators in the blood of women with PCOS without and with metabolic syndrome (MS) and their dependency on lipids, comparing with healthy women. To our knowledge, this is the first study on this topic. METHODS: This was a cross-sectional study, and blood tests performed were double-blind. Within 3 months, 205 PCOS patients, from whom 55 also had MS, and 65 healthy women (control) were recruited. Malondialdehyde (MDA) was assessed as an important oxidative indicator, and superoxide dismutase (SOD), total antioxidant activity (TAA), vitamin C (VC), vitamin E (VE) and retinol (RET) as antioxidative indicators. Their correlation with features of MS was analyzed including their dependency on lipid pattern. RESULTS: SOD, TAA, VE and RET in the PCOS group and PCOS + MS group were lower and MDA higher than in the control group (p < 0.05). SOD, VE and RET were the lowest in PCOS + MS group (p < 0.05). Thus, patients in this group had the highest oxidative stress levels but the lowest antioxidative capacity. SOD and TAA significantly decreased with increase of triglycerides (TG) and LDL-C in the PCOS + MS group (p < 0.05), but without dependency on HDL-C. Stepwise multiple linear regression analysis confirmed the different expression of oxidative stress in the three groups and decrease of SOD from control to PCOS group to PCOS + MS group, being associated with an increase of TG. CONCLUSIONS: MS can accelerate the oxidative stress process in patients with PCOS and decrease the antioxidative capacity. The decreased antioxidant capacity in PCOS with MS is related to increased TG and LDL-C.

Effect of orlistat or metformin in overweight and obese polycystic ovary syndrome patients with insulin resistance.

The aim of this study was to evaluate the effect of orlistat or metformin combined with Diane-35 on anthropometric, hormonal and metabolic parameters in overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance (fasting insulin > 10 mIU/L). A total of 240 PCOS women were randomly allocated to orlistat plus Diane-35(OD group), metformin plus Diane-35(MD group), orlistat plus metformin plus Diane-35(OMD group) or Diane-35 (D group). Body weight, BMI, waist and hip circumference, blood pressure, endocrine profile, lipid profile and insulin resistance were assessed at baseline and after 3 months. Significant reductions in waist and hip circumference, serum LH, total testosterone and uric acid were observed in all groups compared with baseline. TG and TC significantly decreased in the OD group. Homeostasis model assessment insulin resistance (HOMA-IR) index was reduced in the OD (p = .015), MD (p = .001) and OMD (p = .004) groups. Body weight, BMI, systolic BP and HDL-C significantly changed in the OD and OMD group compared with the D group (p < .05). Side effects were less with orlistat than metformin. This study demonstrated that orlistat is more effective in reducing weight and lipid profile than metformin. Besides, orlistat has mild side-effects and is better tolerated compared with metformin.

Effect of Diane-35, alone or in combination with orlistat or metformin in Chinese polycystic ovary syndrome patients.

OBJECTIVE: To evaluate the effect of Diane-35, alone or in combination with orlistat or metformin, on androgen and body fat percentage parameters in Chinese overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance. METHODS: A total of 240 PCOS women were randomly allocated to receive Diane-35 alone (D group), Diane-35 plus orlistat (DO group), Diane-35 plus metformin (DM group), or Diane-35 plus orlistat plus metformin (DOM group). Serum TT, DHEA-S, androstenedione, SHBG, FT, FAI, body fat, and body fat percentage were assessed at baseline and after 12 weeks of treatment. RESULTS: Significant changes in serum TT, SHBG, and FAI were observed in all treatment groups compared with baseline. DHEA-S and androstenedione significantly decreased in the DO, DM, and DOM groups after treatment. FT only significantly decreased in the DOM group. Body fat and body fat percentage significantly decreased in the DO and DOM groups. Compared with the D group, DHEA-S significantly decreased in the DO, DM, and DOM groups (F = 4.081, p = 0.008); SHBG significantly increased in the DOM group (F = 3.019, p = 0.031); and FAI significantly decreased in the DO group (χ2 = 12.578, p = 0.006). There were significant differences between groups in body fat percentage (χ2 = 23.590, p < 0.001). Side-effects were less with orlistat than metformin. CONCLUSIONS: Diane-35 in combination with orlistat or metformin is more effective in reducing androgen than Diane-35 alone. Orlistat is more effective in reducing body fat percentage than metformin. In addition, orlistat has mild side-effects and is better tolerated compared with metformin.

Defect width: the prognostic index for vaginal repair of cesarean section diverticula.

PURPOSE: To evaluate the clinical parameter associated with cesarean section diverticula anatomic healing via vaginal repair management. METHODS: Observational cohort study. From Jul 2014 to Dec 2015, 143 women with CSD underwent vaginal repair surgery in Shanghai First Maternity and Infant Hospital, and 137(95.80%) were diagnosed using both transvaginal ultrasound and MRI. A total of 124 patients (86.71%) who were followed-up for more than 6 months after surgery were enrolled in this study. Excision and suture of CSD was performed through the vaginal approach. The defect sizes of the width, length, depth and TRM before or after repair were evaluated. RESULTS: The mean preoperative duration of menstruation was 14.47 ± 3.30 days and the thickness of the remaining muscular layer was 2.65 ± 1.13 mm before surgery. The study revealed that the healing effects of CSD repair stabilized 3 months after surgery. At the median follow-up time (11.28 months), CSD disappeared after surgery in 64.52% of patients (80/124), and 60.0% of patients (48/80) reached ≤7 days of menstruation. Meanwhile, for 35.48% of patients (44/124), CSD persisted at the median follow-up after surgery, and 31.82% (14/44) of these patients reached ≤7 days of menstruation(P < 0.05). TRM at a median follow-up time after vaginal repair >7.88 mm, 92.11% (70/76) of CSD disappeared. Moreover, when preoperative CSD width ≤18.85 mm indicates that only 18.75% (12/64) of patients will present with CSD after vaginal repair, as determined by MRI (95% CI 0.515-0.737). CONCLUSION: The defect width of the preoperative CSD was the prognostic index of CSD anatomical repair effect. When the preoperative CSD width >18.85 mm, we should pay more attention to the edge of the defect during vaginal repairing.

Vaginal Repair of Cesarean Section Scar Diverticula that Resulted in Improved Postoperative Menstruation.

STUDY OBJECTIVE: Owing to the increase in cesarean sections (C-sections) worldwide, long-term complications such as postmenstrual spotting, chronic pelvic pain, and C-section scar ectopic pregnancies have created a new medical era of gynecologic disease. A new type of vaginal repair is evaluated to repair C-section diverticulum (CSD) and rebuild the muscular layer to improve symptoms of abnormal uterine bleeding and decrease the risk of uterine rupture. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: A total of 121 patients with CSD diagnoses by transvaginal ultrasound (TVU) presented with postmenstrual spotting between June 2012 and March 2015. All patients had undergone at least 1 C-section delivery and had no history of postmenstrual spotting before undergoing C-section. INTERVENTION: Vaginal excision and suture of CSD. MEASUREMENT AND MAIN RESULTS: The mean duration of menstruation was 14.87 ± 3.46 days preoperatively and decreased to 8.22 ± 2.73 days at 1 month after surgery, 8.89 ± 2.67 days at 3 months after surgery, and 9.02 ± 2.47 days at 6 months after surgery (p < .01). The length, width, depth, and thickness of the remaining muscular layer (TRM) at 1 month, 3 months, and 6 months assessed by TVU also improved significantly after surgery (p < .05). However, postoperative menstruation and imaging data did not differ markedly between 3 months and 6 months, suggesting that follow-up at 3 months represents an adequate endpoint for evaluating the effectiveness of surgery. At 6 months, 80.3% of patients (94 of 117) reached ≤10 days of menstruation. Further study revealed that a TRM at 6 months of ≥8.5 mm measured by TVU (relative risk [RR], 6.418; 95% confidence interval [CI], 1.478-28.443) and an interval between CS and vaginal repair of ≤2.5 years (RR, 12.0; 95% CI, 1.541- 93.454) were good prognostic factors associated with surgery. CONCLUSION: Vaginal repair of CSD improved the symptoms of postmenstrual spotting and anatomically corrected the scars. An interval between C-section and a surgery of ≤2.5 years was optimal for vaginal repair, and a TRM at 6 months of ≥8.5 mm represented the standard healing of CSD.

Effects of hypoxia-preconditioned HucMSCs on neovascularization and follicle survival in frozen/thawed human ovarian cortex transplanted to immunodeficient mice.

BACKGROUND: The massive loss of follicles in the early stage of ovarian tissue transplantation is considered a significant restriction to the efficacy of ovarian tissue cryopreservation (OTC) and transplantation (OT). The use of mesenchymal stem cells (MSCs) before transplantation of ovarian fragments shortened the hypoxic period and boosted neovascularization. Hypoxia-preconditioned MSCs can enhance the potential of angiogenesis. Can hypoxia-preconditioned human umbilical cord mesenchymal stem cell (HucMSCs) and ovarian tissue co-xenotransplantation improve more neovascularization and subsequently more follicle survival in human ovarian tissue? METHODS: Frozen-thawed cortical pieces from 4 patients were transplanted into the bilateral renal capsule of immune-deficient nude mice without HucMSCs or normoxia/hypoxia-preconditioned HucMSCs. Sixty-four mice were randomly distributed into 4 groups. In each group, the mice were euthanized for blood and/or graft retrieval on post-transplantation days 3 (n = 8) and 7 (n = 8), respectively. Non-grafted frozen-thawed ovarian fragment was taken for non-grafted control. Grafts were histologically processed and analysed for follicle density and atretic follicles by HE, neovascularization by CD34 and CD31 immunohistochemical staining, primordial follicle growth by Ki67 staining, and apoptosis of stromal cell and follicles by immunofluorescence using TUNEL. The ROS and TAC levels of grafted and non-grafted tissue were assessed. We evaluated the protein expression of HIF1α, VEGFA, pAkt, Akt, and GDF9 in grafted and non-grafted ovarian tissue. E2, Prog, AMH, and FSH levels in the plasma of mice were measured after 3 and 7 days of OT. RESULTS: Hypoxia-preconditioned HucMSCs positively protect the grafted ovarian tissue by significantly decreasing the apoptosis and increasing higher expression of CD31, CD34, and VEGFA for earlier angiogenesis. They are crucial to preserving the resting primordial follicle pool by modulation of follicle death. CONCLUSION: This is the first study to demonstrate that co-transplantation of hypoxia-preconditioned HucMSC with ovarian tissue improved earlier vascularization of ovarian grafts in the early post-grafting period, which correlates with increased follicle survival and reduced apoptosis. The HIF1α/VEGFA signal pathways may play an important role in elucidating the mechanisms of action of hypoxia-preconditioned HucMSCs with regard to OT and clinical implementation.

Nb and Mn Co-Modified Na0.5Bi4.5Ti4O15 Bismuth-Layered Ceramics for High-Frequency Transducer Applications.

Lead-free environmentally friendly piezoelectrical materials with enhanced piezoelectric properties are of great significance for high-resolution ultrasound imaging applications. In this paper, Na0.5Bi4.5Ti3.86Mn0.06Nb0.08O15+y (NBT-Nb-Mn) bismuth-layer-structured ceramics were prepared by solid-phase synthesis. The crystallographic structure, micromorphology, and piezoelectrical and electromechanical properties of NBT-Nb-Mn ceramics were examined, showing their enhanced piezoelectricity (d33 = 33 pC/N) and relatively high electromechanical coupling coefficient (kt = 0.4). The purpose of this article is to describe the development of single element ultrasonic transducers based on these piezoelectric ceramics. The as-prepared high-frequency tightly focused transducer (ƒ-number = 1.13) had an electromechanical coupling coefficient of 0.48. The center frequency was determined to be 37.4 MHz and the -6 dB bandwidth to be 47.2%. According to the B-mode imaging experiment of 25 µm tungsten wires, lateral resolution of the transducer was calculated as 56 µm. Additionally, the experimental results were highly correlated to the results simulated by COMSOL software. By scanning a coin, the imaging effect of the transducer was further evaluated, demonstrating the application advantages of the prepared transducer in the field of high-sensitivity ultrasound imaging.

The Fibrillin-1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells.

BACKGROUND: Chemotherapy resistance is a primary reason of ovarian cancer therapy failure; hence it is important to investigate the underlying mechanisms of chemotherapy resistance and develop novel potential therapeutic targets. METHODS: RNA sequencing of cisplatin-resistant and -sensitive (chemoresistant and chemosensitive, respectively) ovarian cancer organoids was performed, followed by detection of the expression level of fibrillin-1 (FBN1) in organoids and clinical specimens of ovarian cancer. Subsequently, glucose metabolism, angiogenesis, and chemosensitivity were analyzed in structural glycoprotein FBN1-knockout cisplatin-resistant ovarian cancer organoids and cell lines. To gain insights into the specific functions and mechanisms of action of FBN1 in ovarian cancer, immunoprecipitation, silver nitrate staining, mass spectrometry, immunofluorescence, Western blotting, and FÓ§rster resonance energy transfer-fluorescence lifetime imaging analyses were performed, followed by in vivo assays using vertebrate model systems of nude mice and zebrafish. RESULTS: FBN1 expression was significantly enhanced in cisplatin-resistant ovarian cancer organoids and tissues, indicating that FBN1 might be a key factor in chemoresistance of ovarian cancer. We also discovered that FBN1 sustained the energy stress and induced angiogenesis in vitro and in vivo, which promoted the cisplatin-resistance of ovarian cancer. Knockout of FBN1 combined with treatment of the antiangiogenic drug apatinib improved the cisplatin-sensitivity of ovarian cancer cells. Mechanistically, FBN1 mediated the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) at the Tyr1054 residue, which activated its downstream focal adhesion kinase (FAK)/protein kinase B (PKB or AKT) pathway, induced the phosphorylation of signal transducer and activator of transcription 2 (STAT2) at the tyrosine residue 690 (Tyr690), promoted the nuclear translocation of STAT2, and ultimately altered the expression of genes associated with STAT2-mediated angiogenesis and glycolysis. CONCLUSIONS: The FBN1/VEGFR2/STAT2 signaling axis may induce chemoresistance of ovarian cancer cells by participating in the process of glycolysis and angiogenesis. The present study suggested a novel FBN1-targeted therapy and/or combination of FBN1 inhibition and antiangiogenic drug for treating ovarian cancer.

Ovarian tissue cryopreservation in a patient with breast cancer during pregnancy: a case report.

BACKGROUND: Fertility preservation using ovarian tissue cryopreservation (OTC) in patients with certain diseases, especially those needing chemo- or radiotherapy, is becoming routine in various Western countries. Our hospital is the first and until now the only centre in China to use this method. The question of whether treatment of breast cancer during pregnancy (PrBC) should be similar to non-pregnant young patients with breast cancer is controversial. To our knowledge, this is the first report worldwide to use OTC as fertility preservation for PrBC. CASE PRESENTATION: During the 29th week of pregnancy, a 24-year-old woman underwent needle aspiration cytology of a left breast tumour. Ultrasound and cytology revealed BI-RADS 4a grade. Oncologists recommended termination of the pregnancy. Caesarean section was performed at week 32, and ovarian tissue samples were collected for OTC to preserve fertility and ovarian endocrine function. Twenty-three ovarian cortex slices were cryopreserved. It is estimated that 13,000 follicles were cryopreserved. Breast nodules and sentinel lymph node biopsy suggested invasive micropapillary carcinoma. Neoadjuvant chemotherapy was started within 1 week after diagnosis. After six courses of neoadjuvant chemotherapy, targeted drug therapy and goserelin acetate, left mastectomy and left axillary lymph node dissection were performed. In total, 23 doses of radiotherapy, eight trastuzumab targeted therapy treatments, and 17 pertuzumab + trastuzumab double targeted therapy treatments were performed after breast cancer surgery. Until now, more than 2 years after delivery, the ovarian function still is good, and no signs of a negative impact of OTC have been observed. Goserelin acetate injections, administered every 28 days, are planned to last for the next 5 years. In addition, endocrine therapy with anastrozole was started after breast cancer surgery and also is scheduled for 5 years. CONCLUSION: OTC for fertility preservation in patients with PrBC does not delay breast surgery, radiotherapy or chemotherapy, which is essential for effective treatment of breast cancer. We assess this method as a promising fertility preservation method which was used here for the first time worldwide in a patient who developed breast cancer during pregnancy.

A Comprehensive Risk Assessment Model for Ovarian Cancer Patients with Phospho-STAT3 and IL-31 as Immune Infiltration Relevant Genes.

INTRODUCTION: Ovarian carcinoma is a malignant tumor with a high mortality rate and a lack of effective treatment options for patients at advanced stages. For improving outcomes and helping patients with poor prognosis, choose a suitable therapy and an excellent risk assessment model and new treatment options are needed. MATERIALS AND METHODS: Ovarian cancer gene expression profile of GSE32062 was downloaded from the NCBI GEO database for screening differentially expressed genes (DEGs) between well and poor prognosis groups using limma package in R (version 3.4.1). Prognosis-related genes and clinical prognostic factors were obtained from univariate and multivariate Cox regression analyses, and a comprehensive risk assessment model was constructed using a Pathway Dysregulation Score (PDS) matrix, Cox-Proportional Hazards (Cox-PH) regression, as well as L1-least absolute shrinkage and selection operator (L1-LASSO) penalization. Then, significant DEGs were converted to pathways and optimal prognosis-related pathways were screened. Finally, risk prediction models based on pathways, genes involved in pathways, and comprehensive clinical risk factors with pathways were built. Their prognostic functions were assessed in verification sets. Besides, genes involved in immune-pathways were checked for immune infiltration using immunohistochemistry. RESULTS: A superior risk assessment model involving 9 optimal combinations of pathways and one clinical factor was constructed. The pathway-based model was found to be superior to the gene-based model. Phospho-STAT3 (from JAK-STAT signaling pathway) and IL-31 (from DEGs) were found to be related to immune infiltration. CONCLUSION: We have generated a comprehensive risk assessment model consisting of a clinical risk factor and pathways that showed a possible bright foreground. The set of significant pathways might play as a better prognosis model which is more accurate and applicable than the DEG set. Besides, p-STAT3 and IL-31 showing correlation to immune infiltration of ovarian cancer tissues may be potential therapeutic targets for treating ovarian cancers.

Development of a nomogram to predict prognosis in ovarian cancer: a SEER-based study.

BACKGROUND: Ovarian cancer remains the most lethal gynecologic malignancy. In this study, we aimed to identify the specific risk factors affecting overall survival (OS) and develop a nomogram for prognostic prediction of ovarian cancer patients based on data from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Information from the SEER database on ovarian cancer between 2004 and 2016 was screened and retrieved. Cases were randomly divided into the training cohort hand the validation cohort at a 7:3 ratio. The prognostic effects of individual variables on survival were evaluated via Kaplan-Meier method and Cox proportional hazards regression model using data from the training cohort. A nomogram was formulated to predict the 3- and 5-year OS rates of patients with ovarian cancer, and then validated both in the training cohort and the validation cohort. RESULTS: A total of 28,375 patients were selected from 75,921 samples (19,862 in training cohort and 8,513 in validation cohort). Cox regression analysis identified race, age laterality, histology, stage, grade, surgery, chemotherapy, radiotherapy, and marital status as independent risk factors for ovarian cancer prognosis. A nomogram was developed based on the results of multivariate analysis and validated using an internal bootstrap resampling approach, which demonstrated a sufficient level of discrimination according to the C-index (0.752, 95% CI: 0.746-0.758 in the training cohort, 0.755, 95% CI: 0.746-0.764). CONCLUSIONS: We developed a nomogram valuable for accurate prediction of 3- and 5-year OS rates of ovarian cancer patients based on individual characteristics.