[Exploration of factors for failure of non-invasive prenatal testing based on Logistic regression analysis].

OBJECTIVE: To explore the factors for the failure of non-invasive prenatal testing (NIPT) through multifactorial unconditional Logistic regression analysis. METHODS: A total of 3 410 pregnant women who had visited Dalian Women and Children Medical Group from July 2019 to June 2020 were selected as the study subjects and divided into first success NIPT group (n = 3 350) and first failed group (n = 60). Clinical data including age, weight, body mass index (BMI), gestational week, type of pregnancy (singleton/twin), history of delivery, heparin treatment, and conception method [natural conception/assisted reproductive technology (ART)] were collected. Independent sample t-test and Chi-square test were carried out for comparing the two groups, and multi-factorial unconditional Logistic regression analysis was carried out to explore the factors for the failure of NIPT, and receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnosis and predictive effects. RESULTS: Among the 3 410 pregnant women, 3 350 were assigned to the first success NIPT group, and 60 were assigned to the first failed group, and the first-time failure rate was 1.76% (60/3 410). No significant difference was found in age, weight, BMI and method of conception between the two groups (P > 0.05). Compared with first success group, first failed group had lower sampling gestational weeks, lower proportion of women with previous history of delivery, and higher proportion of twin pregnancies and heparin treatment (P < 0.05). Multi-factorial unconditional Logistic regression analysis indicated that sampling gestational week (OR = 0.931, 95%CI: 0.845 ~ 1.026, P < 0.001) and history of heparin use (OR = 8.771, 95%CI: 2.708 ~ 28.409, P < 0.001) are independent factors for first failed NIPT. One-way unconditional Logistic regression analysis for sampling gestational weeks indicated that the regression equation for NIPT screening failure was Logit (P) = -9.867 + 0.319 × sampling gestational week, with the area under the ROC curve being 0.742, a Jordan index of 0.427, and a cutoff value of 16.36 weeks. CONCLUSION: Gestational week and heparin treatment are independent factors for the first failed NIPT. A regression equation has been established and determined the optimal sampling gestational week to be 16.36 weeks, which may provide a reference for the timing of NIPT screening.

Identification of characteristic metabolic panels for different stages of prostate cancer by 1H NMR-based metabolomics analysis.

BACKGROUND: Prostate cancer (PCa) is the second most prevalent cancer in males worldwide, yet detecting PCa and its metastases remains a major challenging task in clinical research setups. The present study aimed to characterize the metabolic changes underlying the PCa progression and investigate the efficacy of related metabolic panels for an accurate PCa assessment. METHODS: In the present study, 75 PCa subjects, 62 PCa patients with bone metastasis (PCaB), and 50 benign prostatic hyperplasia (BPH) patients were enrolled, and we performed a cross-sectional metabolomics analysis of serum samples collected from these subjects using a 1H nuclear magnetic resonance (NMR)-based metabolomics approach. RESULTS: Multivariate analysis revealed that BPH, PCa, and PCaB groups showed distinct metabolic divisions, while univariate statistics integrated with variable importance in the projection (VIP) scores identified a differential metabolite series, which included energy, amino acid, and ketone body metabolism. Herein, we identified a series of characteristic serum metabolic changes, including decreased trends of 3-HB and acetone as well as elevated trends of alanine in PCa patients compared with BPH subjects, while increased levels of 3-HB and acetone as well as decreased levels of alanine in PCaB patients compared with PCa. Additionally, our results also revealed the metabolic panels of discriminant metabolites coupled with the clinical parameters (age and body mass index) for discrimination between PCa and BPH, PCaB and BPH, PCaB and PCa achieved the AUC values of 0.828, 0.917, and 0.872, respectively. CONCLUSIONS: Overall, our study gave successful discrimination of BPH, PCa and PCaB, and we characterized the potential metabolic alterations involved in the PCa progression and its metastases, including 3-HB, acetone and alanine. The defined biomarker panels could be employed to aid in the diagnosis and classification of PCa in clinical practice.

Association of ADAMTS proteoglycanases downregulation with IVF-ET outcomes in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) is involved in inflammation and fertility in women with polycystic ovary syndrome (PCOS). This study aims to assess the role of ADAMTS level in the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with PCOS, using a meta-analytic approach. METHODS: We systematically searched Web of Science, PubMed, EmBase, and the Cochrane library to identify potentially eligible studies from inception until December 2021. Study assess the role of ADAMTS levels in patients with PCOS was eligible in this study. The pooled effect estimates for the association between ADAMTS level and IVF-ET outcomes were calculated using the random-effects model. RESULTS: Five studies involving a total of 181 patients, were selected for final analysis. We noted that ADAMTS-1 levels were positively correlated to oocyte maturity (r = 0.67; P = 0.004), oocyte recovery (r = 0.74; P = 0.006), and fertilization (r = 0.46; P = 0.041) rates. Moreover, ADAMTS-4 levels were positively correlated to oocyte recovery (r = 0.91; P = 0.001), and fertilization (r = 0.85; P = 0.017) rates. Furthermore, downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 was associated with elevated follicle puncture (ADAMTS-1: weighted mean difference [WMD], 7.24, P < 0.001; ADAMTS-4: WMD, 7.20, P < 0.001; ADAMTS-5: WMD, 7.20, P < 0.001; ADAMTS-9: WMD, 6.38, P < 0.001), oocytes retrieval (ADAMTS-1: WMD, 1.61, P < 0.001; ADAMTS-4: WMD, 3.63, P = 0.004; ADAMTS-5: WMD, 3.63, P = 0.004; ADAMTS-9: WMD, 3.20, P = 0.006), and Germinal vesicle oocytes levels (ADAMTS-1: WMD, 2.89, P < 0.001; ADAMTS-4: WMD, 2.19, P < 0.001; ADAMTS-5: WMD, 2.19, P < 0.001; ADAMTS-9: WMD, 2.89, P < 0.001). Finally, the oocytes recovery rate, oocyte maturity rate, fertilization rate, cleavage rate, good-quality embryos rate, blastocyst formation rate, and clinical pregnancy rate were not affected by the downregulation of ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-9 (P > 0.05). CONCLUSIONS: This study found that the outcomes of IVF-EF in patients with PCOS could be affected by ADAMTS-1 and ADAMTS-4; further large-scale prospective studies should be performed to verify these results.

Association between preconception serum lipid concentrations and treatment outcomes in women with PCOS who underwent ovulation induction.

RESEARCH QUESTION: What is the association between preconception serum lipid concentrations and reproductive outcomes after ovulation induction in women with polycystic ovary syndrome (PCOS)? DESIGN: A secondary analysis of a randomized controlled trial with 1000 PCOS women undergoing ovulation induction with clomiphene with or without acupuncture. Preconception serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) were measured. Outcomes were ovulation, conception, pregnancy, live birth and miscarriage. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: In total, 780 women ovulated; 320 women achieved conception, 218 had a clinical pregnancy, 205 had a live birth and 115 had a miscarriage. Serum lipid concentrations per one unit increment were independently associated with reproductive outcomes after controlling for confounders. Increasing LDL-C (OR 0.79, 95% CI 0.63-0.99) was independently associated with a lower chance of ovulation. Increasing total cholesterol (OR 0.76, 95% CI 0.62-0.92), LDL-C (OR 0.73, 95% CI 0.57-0.93), triglycerides (OR 0.74, 95% CI 0.58-0.95) and ApoB (OR 0.34, 95% CI 0.16-0.74) were independently associated with a lower chance of clinical pregnancy. Increased total cholesterol (OR 0.78, 95% CI 0.64-0.96), LDL-C (OR 0.77, 95% CI 0.60-0.99), triglycerides (OR 0.76, 95% CI 0.59-0.96) and ApoB (OR 0.39, 95% CI 0.18-0.86) were independently associated with a lower chance of live birth. Furthermore, increased total cholesterol (OR 1.43, 95% CI 1.06-1.93), LDL-C (OR 1.51, 95% CI 1.04-2.19) and ApoB (OR 3.82, 95% CI 1.17-12.41) were independently associated with a higher chance of miscarriage. CONCLUSIONS: Increased serum lipids were negatively associated with the reproductive outcomes of PCOS women undergoing ovulation induction with clomiphene with or without acupuncture.

PGT-A: The biology and hidden failures of randomized control trials.

OBJECTIVE: Preimplantation Genetic Testing - Aneuploidy (PGT-A) for embryo selection has undergone significant advancements in the last 2 decades and yet many studies still fail to demonstrate any clinical benefits over traditional embryo morphology selection (Mo-S). To understand this conundrum, we performed a multi-center clinical study of PGT-A patients, where Mo-S and euploid selection (Eu-S) outcomes were directly compared. METHOD: All suitable blastocysts were biopsied and analyzed for chromosome copy number. Outcomes (positive beta hCG, implantation, ongoing pregnancy, and live birth rates) for Eu-S were compared to Mo-S using single embryo transfers. RESULTS: Compared to Eu-S embryos, Mo-S embryos resulted in significant reduction of outcomes for positive beta hCG (p = 0.0005), implantation (p = 0.0008), ongoing pregnancy (p = 0.0046), livebirth (p = 0.0112), babies per transfer (p = 0.0112), and babies per embryo transferred (p = 0.0112). Morphology selection resulted in patients of all age groups having non-euploid embryos chosen for transfer. Post-hoc evaluation of individual clinic performances showed variable transfer outcomes that could potentially confound the true benefits of PGT-A. CONCLUSION: Embryo chromosome status is central to improved embryo transfer outcomes and sole reliance on current morphology-based selection practices, without Eu-S, will always compromise outcomes. Often overlooked but a major effector of successful PGT-A outcomes are individual clinic performances.

Ginkgo biloba extract 761 reduces vascular permeability of the ovary and improves the symptom of ovarian hyperstimulation syndrome in a rat model.

AIMS: Ginkgo biloba extract (EGb) has been widely applied in the treatment of cerebrovascular and neurological diseases. However, the effect of EGb761 on ovarian hyperstimulation syndrome (OHSS), a vascular disorder and life-threatening complication of in vitro fertilization and intracytoplasmic sperm injection therapy (IVF/ICSI), has not been evaluated. MATERIALS AND METHODS: Forty female Wistar rats aged 22-days old (D22) were divided into eight groups: Control rats received intraperitoneal injection of saline for five consecutive days (D22-D26); OHSS model group received 10 IU equine chorionic gonadotropin (eCG) for four consecutive days (D22-D25) and 30 IU of human chorionic gonadotropin (hCG) on the 5th day (D26); Prophylactic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/day) 1 h before injection of eCG (hCG) for seven consecutive days; Therapeutic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/day) 48 h after injection of eCG (hCG) for seven consecutive days. RESULTS: All three doses of EGb761 therapeutic medication significantly reduced ovarian mass index of OHSS model rats (p ≤ .01). Furthermore, therapeutic treatment group exhibited improved vascular permeability, decreased estradiol and progesterone levels, lower corpus luteum, and higher follicle numbers compared with the OHSS model. Elevated protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) in both ovary and kidney of the OHSS model was restrained by EGb761 therapeutic treatment. CONCLUSIONS: EGb761 therapeutic medication decreases vascular permeability in OHSS rat model by inhibiting VEGF and VEGFR expression, which may contribute to the treatment of OHSS.

Ginkgo biloba extract 761 reduces vascular permeability of the ovary and improves the symptom of ovarian hyperstimulation syndrome in a rat model.

AIMS: Ginkgo biloba extract (EGb) has been widely applied in the treatment of cerebrovascular and neurological diseases. However, the effect of EGb761 on ovarian hyperstimulation syndrome (OHSS), a vascular disorder and life-threatening complication of In Vitro Fertilization and Intracytoplasmic Sperm Injection therapy (IVF/ICSI), has not been evaluated. MATERIALS AND METHODS: Forty female Wistar rats aged 22-days old (D22) were divided into eight groups: Control rats received intraperitoneal injection of saline for 5 consecutive days (D22-D26); OHSS model group received 10 IU equine chorionic gonadotropin (eCG) for 4 consecutive days (D22-D25) and 30 IU of human chorionic gonadotropin (hCG) on the 5th day (D26); Prophylactic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/d) one hour before injection of eCG (hCG) for 7 consecutive days; Therapeutic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/d) 48 h after injection of eCG (hCG) for 7 consecutive days. RESULTS: All three doses of EGb761 therapeutic medication significantly reduced ovarian mass index in the OHSS model (p ≤ .01). Further, the therapeutic treatment group exhibited improved vascular permeability, decreased estradiol and progesterone levels, lower corpus luteum, and higher follicle numbers compared with the OHSS model. Elevated protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) in both ovary and kidney of the OHSS model was restrained by EGb761 therapeutic treatment. CONCLUSIONS: EGb761 therapeutic medication decreases vascular permeability in OHSS rat model by inhibiting VEGF and VEGFR expression, which may contribute to the treatment of OHSS.

IVF embryo choices and pregnancy outcomes.

OBJECTIVE: Investigate the chromosome status and transfer outcomes of embryos selected using routine "best morphology" IVF practices. METHOD: A prospective multi-center, non-selection cohort study involving patients undertaking IVF treatment. Study entry conditions were blastocyst biopsy, >1 embryo with chromosome analysis and frozen transfer of the best morphology embryo. Primary analyses were ßhCG positive, implantation, ongoing pregnancy and birth rates and pregnancy-stage progression failures. RESULTS: After transfer, embryo chromosome status was assigned and outcomes divided into two primary groups - euploids (n = 135) and aneuploids (n = 53). Compared to euploid embryo transfers, aneuploid embryos had significantly lower primary outcomes (+ßhCG: 67% vs. 30%, p < 0.0001; IR: 56% vs. 19%, p < 0.0001; ongoing week 12: 51% vs. 9%, p < 0.0001; and livebirths: 50% vs. 8%, p < 0.0001, respectively). Transfers were further subdivided into smaller groups according to their main chromosomal feature. Stage analysis showed higher failure rates for aneuploids to initiate a pregnancy (p < 0.0001), higher subclinical miscarriage rate (p = 0.0402) and higher clinical miscarriage rate (p = 0.0038). CONCLUSION: Routine morphology-based embryo selection resulted in a high euploid selection rate but a significant number of aneuploid embryos were still inadvertently selected for transfer (28%) with the subsequent high failure rates for pregnancy initiation and progression having implications for appropriate patient management.

Distinct Metabolic Signatures of Hormone-Sensitive and Castration-Resistant Prostate Cancer Revealed by a 1H NMR-Based Metabolomics of Biopsy Tissue.

Tumor metabolic characteristics have been associated with the progression of prostate cancer (PCa), but little information is available regarding the metabolic alterations from hormone-sensitive (HSPC) to castration-resistant PCa (CRPC). In this study, therefore, we investigated the metabolic profiles in prostate tissues from patients with benign prostatic hyperplasia (BPH), HSPC, and CRPC using a 1H NMR-based metabolomics approach. The results show that clear separations in metabolic patterns were obtained in prostate tissues among BPH, HSPC, and CRPC; however, CRPC may induce a metabolic shift toward BPH, mainly involving amino acid metabolism, choline metabolism, and the Warburg effect. Based on these metabolic changes, we identified potential biomarker panels for the discrimination between BPH vs HSPC, BPH vs CRPC, and HSPC vs CRPC with the AUC values of 0.995, 0.972, and 0.937, respectively. Collectively, tissue-based metabolomics analysis not only identifies the altered metabolic pathways during PCa progression but also has the potential to help the classification and diagnosis of PCa in clinical practice.

Deep convolutional neural networks combine Raman spectral signature of serum for prostate cancer bone metastases screening.

Prostate cancer most frequently metastasizes to bone, resulting in abnormal bone metabolism and the release of components into the blood stream. Here, we evaluated the capacity of convolutional neural networks (CNNs) to use Raman data for screening of prostate cancer bone metastases. We used label-free surface-enhanced Raman spectroscopy (SERS) to collect 1281 serum Raman spectra from 427 patients with prostate cancer, and then we constructed a CNN based on LetNet-5 to recognize prostate cancer patients with bone metastases. We then used 5-fold cross-validation method to train and test the CNN model and evaluated its actual performance. Our CNN model for bone metastases detection revealed a mean training accuracy of 99.51% ± 0.23%, mean testing accuracy of 81.70% ± 2.83%, mean testing sensitivity of 80.63% ± 5.07%, and mean testing specificity of 82.82% ± 2.94%.

Systemic immune-inflammation index predicts the combined clinical outcome after sequential therapy with abiraterone and docetaxel for metastatic castration-resistant prostate cancer patients.

OBJECTIVE: To compare the antitumor effect of abiraterone (AA) followed by docetaxel-prednisone (DP) or vice versa in metastatic castration-resistant prostate cancer (mCRPC) patients, and explored factors that might predict combined PSA-PFS, combined rPFS and OS. PATIENTS AND METHODS: We retrospectively analyzed mCRPC patients treated with sequential therapy using DP followed by AA or vice versa. Patients who had received enzalutamide or cabazitaxel were excluded. The primary outcome measure was overall survival (OS). The combined PSA progression-free survival (PSA-PFS), combined radiographic PFS (rPFS), and OS of AA-to-DP were compared to the reverse sequence using Kaplan-Meier curves with log-rank statistics. Univariable and multivariable Cox regression analyses were performed to determine prognostic factors that were associated with combined PSA-PFS, combined rPFS and OS. RESULTS: A total of 104 mCRPC patients who began treatment between 2013 and 2017 were identified: 42 were in the DP-to-AA group and 62 were in the AA-to-DP group. There was no significant difference of baseline clinical characteristics between AA-to-DP and DP-to-AA group. In addition, there was no significant difference in combined PSA-PFS (AA-to-DP: 12.5 [11.4-13.6] vs DP-to-AA: 13.2 [10.9-15.5] months [P = 0.127]), combined rPFS (AA-to-DP: 12.2 [10.9-13.4] vs DP-to-AA: 11.2 [8.9-13.5] months [P = 0.183]) and OS (AA-to-DP: 23.3 [19.7-26.9] vs DP-to-AA: 22.9 [22.1-23.7] months [P = 0.213]) between the two treatment sequences in Kaplan-Meier analysis. In multivariate Cox regression analysis, high systematic Immune-Inflammation Index (SII) level, which was calculated by P (platelet) × N (neutrophil)/L(lymphocyte), remained significant predictors of OS, combined rPFS and combined PSA-PFS. CONCLUSION: In this study, we did not observe differences in clinical outcomes based on alternative sequencing of AA and DP in mCRPC patients. The ability to tolerate side effects and patient preference may be used to determine the treatment sequencing. In addition, high pretreatment SII level is a negative independent prognosticator of survival outcomes in mCRPC with sequential therapy using DP followed by AA or vice versa, which might guide clinicians select the best treatment.

Assessment of the development of assisted reproductive technology in Liaoning province of China, from 2012 to 2016.

BACKGROUND: The development of assisted reproduction techniques (ART) has resulted in rapid advances in the treatment of infertility. However, a systematic assessment of ART and its processes and outcomes in China has never been carried out. The goal of this study was to assess the features of ART status from 2012 to 2016 in clinics and in vitro fertilization (IVF) laboratories in Liaoning, the largest IVF province in the northeast of China. METHODS: Data from Jan 1, 2012 to Dec 31, 2016 was retrieved from the assisted reproductive certificate registry of Liaoning province. We extracted data from: i) fresh and thawed cycles; ii) donor sperm and donor egg cycles; iii) intrauterine insemination with husband semen and donor semen (AIH and AID). RESULTS: We showed that: (i) there has been a significant increase in the number of IVF fresh and thawed cycles, and the proportion of cases of primary infertility and secondary infertility has decreased and increased, respectively; (ii) standard long GnRH agonist was the major ovarian stimulation protocol. During the observation period, increasing trends in the use of GnRH antagonists, mild stimulation, and natural cycles were observed; (iii) significant differences in the number of cycles, number of retrieved oocytes, fertilization rates, implantation rates, and sex ratio were noticed between conventional IVF and intracytoplasmic sperm injection; (iv) significant differences in age at treatment for infertility, number of cycles, and ectopic pregnancy rates were noticed between donor sperm cycles and donor egg cycles; (v) significant differences in number of thawed cycles, number of thawed embryos, embryo recovery rates, implantation rates, and clinical pregnancy rates were noticed between day 3 and day 5 embryos; (vi) significant differences in age at treatment for infertility, number of cycles, clinical pregnancy rates, ectopic pregnancy rates, and live birth ratio were noticed between AIH and AID. CONCLUSIONS: ART in Liaoning province has undergone substantial development from 2012 to 2016 in clinics and IVF laboratories. This presentation of detailed ART data will provide researchers, policy makers, and potential ART users a rich source of information about IVF characteristics in the northeast of China.

Prognostic nutritional index predicts initial response to treatment and prognosis in metastatic castration-resistant prostate cancer patients treated with abiraterone.

OBJECTIVE: To determine if prognostic nutritional index (PNI) and its variation could predict initial response to treatment and prognosis in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Abiraterone (AA). PATIENTS AND METHODS: One-hundred-twelve chemotherapy pretreated or chemotherapy-naive patients were scheduled for systemic treatment with AA. PNI levels were measured before and after one month of AA treatment. Univariate and multivariate logistic regression analyses were used to identify predictive factors of initial response to AA treatment. Univariable and Multivariable Cox regression analyses were performed to determine prognostic factors that were associated with PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS). The Harrell concordance index with variables only or combined PNI data were used to evaluate the prognostic accuracy. RESULTS: Eighty-one (72.3%) of 112 patients showed initial response to AA treatment, in which 15 experienced PSA flare during AA treatment. In multivariate logistic regression analyses, high baseline PNI level, PSA level decrease during the first month of AA treatment and PNI level elevation during the first month of AA treatment were significantly correlated with initial response to AA treatment. In multivariate Cox regression analysis, low PNI level remained significant predictors of OS, rPFS and PSA-PFS. The estimated c-index of the multivariate model for OS increased from 0.82 without PNI to 0.83 when PNI added. CONCLUSION: Independent of PSA level variation, PNI level elevation during the first month of AA treatment and high baseline PNI level were significantly correlated with initial response to AA treatment. In addition, low pretreatment PNI level is a negative independent prognosticator of survival outcomes in mCRPC treated with AA and also increases the accuracy of established prognostic model.

Influence of abiraterone acetate on neuroendocrine differentiation in chemotherapy-naive metastatic castration-resistant prostate cancer.

BACKGROUND: To determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted an analysis in 115 chemotherapy-naïve mCRPC patients who would be treated with chemotherapy. The serum levels of chromogranin A (CgA), neurone-specific enolase (NSE) were measured in 67 mCRPC patients without AA treatment and 48 patients after the failure of AA treatment, in which these markers were also measured in 34 patients before and after 6 months of AA treatment. Comparative t-test was used to evaluate the serial changes of serum NED markers during AA treatment and univariate and multivariate analyses were performed to test the influence of AA treatment on NED. RESULTS: Serum CgA were NSE were evaluated to be above the upper limit of normal (ULN) in 56 (48.7%) and 29 (25.2%) patients before chemotherapy. In 34 patients with serial evaluation, serum CgA level of 14 patients and NSE of 14 patients increased after the failure of AA treatment. There was no significant difference of NED markers (CgA or NSE variation (P = 0.243) between at baseline and after the failure of AA treatment. Compared with the CgA elevation group in the first 6 months of AA treatment and baseline supranormal CgA group, the CgA decline group, and baseline normal CgA group has a much longer median PSA PFS (14.34 vs 10.00 months, P < 0.001, and 14.23 vs 10.30 months, P = 0.02) and rPFS, respectively (18.33 vs 11.37 months, P < 0.001, and 17.10 vs 12.07 months, P = 0.03). In logistic univariate analysis, AA treatment and its duration were not independent factors influencing NED. CONCLUSIONS: We hypothesized that AA might not significantly lead to progression of NED of mCRPC in general. Furthermore, we found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment. Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.

Evaluation of expressed prostatic secretion and serum using surface-enhanced Raman spectroscopy for the noninvasive detection of prostate cancer, a preliminary study.

Surface-enhanced Raman spectroscopy (SERS) involving expressed prostatic secretion (EPS) and serum was investigated; the objective was to determine if this approach could distinguish prostate cancer from benign prostatic hyperplasia. A total of 120 SERS spectra for EPS and 96 spectra for serum were gathered from patients within a prospective contemporary biopsy cohort. Significant differences in spectra between prostate cancer and benign prostatic hyperplasia were tentatively assigned to component changes in EPS and serum samples. Principal component analysis and linear discriminate analysis were utilized to evaluate the spectral data for EPS and serum, to build diagnostic algorithms. The leave-one-out cross-validation method was used to validate the diagnostic algorithms; it revealed diagnostic sensitivities of 75% and 60%, specificities of 75% and 76.5%, and accuracies of 75% and 68% for EPS and serum, respectively. The results suggest that EPS and serum SERS analysis could be a potential tool for prostate cancer detection.

Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

Platelet to lymphocyte ratio as an independent prognostic indicator for prostate cancer patients receiving androgen deprivation therapy.

BACKGROUND: Platelet to Lymphocyte ratio (PLR) is thought to be associated with a worse outcome in multiple types of cancer. However, the prognostic significance of PLR has not been investigated in the prostate cancer (PCa) patients receiving hormonal therapy. The objective of this study was to determine the prognostic value of PLR in PCa patients treated with androgen deprivation therapy (ADT). METHODS: Two-hundred-ninety prostate cancer patients who had undergone ADT as first-line therapy were retrospectively analyzed. The blood cell counts were performed at the time of diagnosis. PLR was calculated as the ratio of platelet count to lymphocyte count. Patients were categorized in two groups using a cut-off point of 117.58 as calculated by the receiver-operating curve analysis. Correlations between PLR and clinical characteristics were analyzed. Meanwhile, univariate and multivariate cox regression analyses were performed to determine the associations of PLR with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Prognostic accuracy was evaluated with the Harrell concordance index. RESULTS: The differences of age, serum prostate-specific antigen (PSA) level, Gleason score, risk stratification and incidence of metastasis between low PLR group (<117.58) and high PLR group (≥117.58) were not statistically significant (p > 0.05). Multivariate analyses identified PLR as an independent prognostic factor for PFS (hazard ratio (HR) = 1.581, p = 0.013), CSS (HR = 1.768, p = 0.037) and OS (HR = 1.650, p = 0.044). The addition of PLR to the final model improved predictive accuracy (c-index: 0.747, 0.801 and 0.768) for PFS, CSS and OS compared with the clinicopathological base model (c-index: 0.730, 0.778 and 0.746), which included Gleason score and incidence of metastasis. CONCLUSIONS: PLR might play a significant role in the prognosis of PCa patients treated with ADT. Thus, we recommend adding PLR to traditional prognostic model to improve the predictive accuracy.

Intracellular ice formation in mouse zygotes and early morulae vs. cooling rate and temperature-experimental vs. theory.

In this study, mature female mice of the ICR strain were induced to superovultate, mated, and collected at either zygote or early morula stages. Embryos suspended in 1 M ethylene glycol in PBS containing 10 mg/L Snomax for 15 min, then transferred in sample holder to Linkam cryostage, cooled to and seeded at 7 °C, and then observed and photographed while being cooled to -70 °C at 0.5-20 °C/min. Intracellular ice formation (IIF) was observed as abrupt ''flashing''. Two types of flashing or IIF were observed in this study. Extracellular freezing occurred at a mean of -7.7 °C. In morulae, about 25% turned dark within ±1 °C of extracellular ice formation (EIF). These we refer to as "high temperature'' flashers. In zygotes, there were no high temperature flashers. All the zygotes flashed at temperatures well below the temperature for EIF. Presumably high temperature flashers were a consequence of membrane damage prior to EIF or damage from EIF. We shall not discuss them further. In the majority of cases, IIF occurred well below -7.7 °C; these we call ''low temperature'' flashers. None flashed with cooling rate (CR) of 0.5 °C/min in either zygotes or morulae. Nearly all flashed with CR of 4 °C/min or higher, but the distribution of temperatures is much broader with morulae than with zygotes. Also, the mean flashing temperature is much higher with morulae (-20.9 °C) than with zygotes (-40.3 °C). We computed the kinetics of water loss with respect to CR and temperature in both mouse zygotes and in morulae based on published estimates of Lp and it is Ea. The resulting dehydration curves combined with knowledge of the embryo nucleation temperature permits an estimate of the likelihood of IIF as a function of CR and subzero temperature. The agreement between these computed probabilities and the observed values are good.

Core fucosylation regulates the ovarian response via FSH receptor during follicular development.

INTRODUCTION: Ovarian low response to follicle-stimulating hormone (FSH) causes infertility featuring hypergonadotropic hypogonadism, ovarian failure, and/or defective ovarian response. OBJECTIVES: N-glycosylation is essential for FSH receptor (FSHR). Core fucosylation catalyzed by fucosyltransferase 8 (FUT8) is the most common N-glycosylation. Core fucosylation level changes between individuals and plays important roles in multiple physiological and pathological conditions. This study aims to elucidate the significance of FUT8 to modulate FSHR function in female fertility. METHODS: Samples from patients classified as poor ovary responders (PORs) were detected with lectin blot and real-time PCR. Fut8 gene knockout (Fut8-/-) mice and FUT8-knockdown human granulosa cell line (KGN-KD) were established and in vitro fertilization (IVF) assay, western blot, molecular interaction, immunofluorescence and immunoprecipitation were applied. RESULTS: Core fucosylation is indispensable for oocyte and follicular development. FSHR is a highly core-fucosylated glycoprotein. Loss of core fucosylation suppressed binding of FSHR to FSH, and attenuated FSHR downstream signaling in granulosa cells. Transcriptomic analysis revealed the downregulation of several transcripts crucial for oocyte meiotic progression and preimplantation development in Fut8-/- mice and in POR patients. Furthermore, loss of FUT8 inhibited the interaction between granulosa cells and oocytes, reduced transzonal projection (TZP) formation and caused poor developmental competence of oocytes after fertilization in vitro. While L-fucose administration increased the core fucosylation of FSHR, and its sensitivity to FSH. CONCLUSION: This study first reveals a significant presence of core fucosylation in female fertility control. Decreased fucosylation on FSHR reduces the interaction of FSH-FSHR and subsequent signaling, which is a feature of the POR patients. Our results suggest that core fucosylation controls oocyte and follicular development via the FSH/FSHR pathway and is essential for female fertility in mammals.

Effect of vaginal microbiota on pregnancy outcomes of women from Northern China who conceived after IVF.

Objective: This study aimed to investigate the correlation between vaginal microbiota and pregnancy outcomes of women who achieved pregnancy via in vitro fertilization (IVF) in Northern China, and to determine a biomarker for evaluation of the risk of preterm births in these women. Methods: In total, 19 women from Northern China women who conceived after IVF and 6 women who conceived naturally were recruited in this study. The vaginal samples of the healthy participants were collected throughout pregnancy, that is, during the first, second, and third trimesters. The V3-V4 region of 16S rRNA was used to analyze the vaginal microbiome, and the bioinformatic analysis was performed using QIIME Alpha and Beta diversity analysis. Results: Either IVF group or Natural conception group, bacterial community diversities and total species number of vagnal samples from who delivered at term were significantly higher than those who delivered before term. Low abundance of vaginal bacteria indicates an increased risk of preterm delivery. Further, more abundant vaginal bacteria was found in first trimesters instead of the next two trimesters. Vignal samples collected during first trimester showed richer differences and more predictive value for pregnancy outcoes. In addition, the diversity of the vaginal bacterial community decreased as the gestational age increased, in all samples. Alloscardovia was only found in participants who conceived after IVF, and the percentage of Alloscardovia in viginal samples of normal delivery group is much higher than the samples from preterm delivery group.Vobrio specifically colonized in vagina of pregnant woman in AFT group (those who conceived after IVF (A), first trimester (F), and delivered at term (T)) and Sporosarcina was detected only in women with AFT and AST (those who conceived after IVF (A), second trimester (S), and delivered at term (T)). These data indicates that Alloscardovia, Vobrio and Sporosarcina have great potential in predicting pregnancy outcomes who pregnanted by vitro fertilization. Conclusions: Vaginal microbiota were more stable in women who conceived naturally and those who carried pregnancy to term. Oceanobacillus might act as a positive biomarker, whereas Sulfurospirillum and Propionispira may act as negative biomarkers for the risk of preterm birth.