Degradation of levofloxacin from antibiotic wastewater by pulse electrochemical oxidation with BDD electrode.

Antibiotic-containing wastewater is a typical biochemical refractory organic wastewater and general treatment methods cannot effectively and quickly degrade the antibiotic molecules. In this study, a novel boron-doped diamond (BDD) pulse electrochemical oxidation (PEO) technology was proposed for the efficient removal of levofloxacin (LFXN) from wastewater. The effects of current density (j), initial pH (pH0), frequency (f), electrolyte types and initial concentration (c0(LFXN)) on the degradation of LFXN were systematically investigated. The degradation kinetics under four different processes have also been studied. The possible degradation mechanism of LFXN was proposed by Density functional theory calculation and analysis of degradation intermediates. The results showed that under the optimal parameters, the COD removal efficiency (η(COD)) was 94.4% and the energy consumption (EEC) was 81.43 kWh·m-3 at t = 120 min. The degradation of LFXN at pH = 2.8/c(H2O2) followed pseudo-first-order kinetics. The apparent rate constant was 1.33 × 10-2 min-1, which was much higher than other processes. The degradation rate of LFXN was as follows: pH = 2.8/c(H2O2) > pH = 2.8 > pH = 7/c(H2O2) > pH = 7. Ten aromatic intermediates were formed during the degradation of LFXN, which were further degraded to F-, NH4+, NO3-, CO2 and H2O. This study provides a promising approach for efficiently treating LFXN antibiotic wastewater by pulsed electrochemical oxidation with a BDD electrode without adding H2O2.

Discovery of immune-related diagnostic biomarkers and construction of diagnostic model in varies polycystic ovary syndrome.

AIMS: The various diagnostic criteria for polycystic ovary syndrome (PCOS) raised problem for PCOS research worldwide. PCOS has been demonstrated to be significantly associated with immune response. We aimed to identify several immune-related biomarkers and construct a nomogram model for diagnosis in PCOS. METHODS: The mRNA expression data were downloaded from Gene Expression Omnibus (GEO) database. Significant immune-related genes were identified to be the biomarkers for the diagnosis of PCOS using random forest model (RF), support vector machine model (SVM) and generalized linear model (GLM). The key biomarkers were selected from the optimal model and were utilized to construct a diagnostic nomogram. Receiver operating characteristic (ROC) curves was used to evaluate diagnostic ability of nomogram. Moreover, the relative proportion of 22 immune cell types was calculated by CIBERSORT algorithm. RESULTS: Four immune-related biomarkers (cAMP, S100A9, TLR8 and IL6R) were demonstrated to be highly expressed in PCOS. The nomogram constructed on the ground of the four key biomarkers showed perfect performance in diagnosis of PCOS, whose AUC were greater than 0.7. Higher infiltrating abundance of neutrophils, resting NK cells and activated dendritic cells were observed in PCOS and were tightly associated with the four key biomarkers. CONCLUSIONS: This study identified several immune-related diagnostic biomarkers for PCOS patients. The diagnostic nomogram constructed based the biomarkers provide a theory foundation for clinical application. Multiple immune cells were associated with the expression of these four biomarkers and might played a vital role in the procession of PCOS.

The influence of polycystic ovarian syndrome on obstetric and neonatal outcomes after frozen-thawed embryo transfer.

RESEARCH QUESTION: Does polycystic ovary syndrome (PCOS) affect pregnancy and neonatal outcomes after frozen-thawed embryo transfers (FET) using hormone replacement therapy (HRT) cycles or stimulated cycles? DESIGN: This was a retrospective cohort study in which singletons born to 1876 women with PCOS and 14,630 women without PCOS under the age of 38 years from 2010 to 2018 were analyzed at a tertiary care academic medical center. The main outcomes were gestational diabetes mellitus (GDM), pregnancy-induced hypertension, preterm premature rupture of membranes (PPROM) and early preterm birth (EPTB). RESULTS: Women with PCOS showed a higher risk of GDM (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.47-1.99), pregnancy-induced hypertension (aOR 1.46, 95% CI 1.13-1.90), PPROM (aOR 1.40, 95% CI 1.02-1.79) and EPTB (aOR 1.51, 95% CI 1.01-2.26) compared with mothers without PCOS. Considering that more PCOS received HRT cycles, subgroup analyses were performed separately for stimulated cycles and HRT cycles. PCOS was not correlated with PPROM and EPTB in the two subgroups. The rate of GDM, pregnancy-induced hypertension and EPTB among women with without PCOS using stimulated cycles appeared to be lower than in women without PCOS using HRT cycles. CONCLUSIONS: Although PCOS indeed confers independent risks for GDM and pregnancy-induced hypertension after FET compared with no PCOS, risks of other adverse outcomes (e.g. PPROM and EPTB) might be exaggerated owing to a higher proportion of HRT cycles used in PCOS.

Classification and Diagnosis of Residual Thyroid Tissue in SPECT Images Based on Fine-Tuning Deep Convolutional Neural Network.

Patients with thyroid cancer will take a small dose of 131I after undergoing a total thyroidectomy. Single-photon emission computed tomography (SPECT) is used to diagnose whether thyroid tissue remains in the body. However, it is difficult for human eyes to observe the specificity of SPECT images in different categories, and it is difficult for doctors to accurately diagnose the residual thyroid tissue in patients based on SPECT images. At present, the research on the classification of thyroid tissue residues after thyroidectomy is still in a blank state. This paper proposes a ResNet-18 fine-tuning method based on the convolutional neural network model. First, preprocess the SPECT images to improve the image quality and remove background interference. Secondly, use the preprocessed image samples to fine-tune the pretrained ResNet-18 model to obtain better features and finally use the Softmax classifier to diagnose the residual thyroid tissue. The method has been tested on SPECT images of 446 patients collected by local hospital and compared with the widely used lightweight network SqueezeNet model and ShuffleNetV2 model. Due to the small data set, this paper conducted 10 random grouping experiments. Each experiment divided the data set into training set and test set at a ratio of 3:1. The accuracy and sensitivity rates of the model proposed in this paper are 96.69% and 94.75%, which are significantly higher than other models (p < 0.05). The specificity and precision rates are 99.6% and 99.96%, respectively, and there is no significant difference compared with other models. (p > 0.05). The area under the curve of the proposed model, SqueezeNet, and ShuffleNetv2 are 0.988 (95% CI, 0.941-1.000), 0.898 (95% CI, 0.819-0.951) (p = 0.0257), and 0.885 (95% CI, 0.803-0.941) (p = 0.0057) (p < 0.05). We prove that this thyroid tissue residue classification system can be used as a computer-aided diagnosis method to effectively improve the diagnostic accuracy of thyroid tissue residues. While more accurately diagnosing patients with residual thyroid tissue in the body, we try our best to avoid the occurrence of overtreatment, which reflects its potential clinical application value.

Comparison Between PPOS and GnRHa-Long Protocol in Clinical Outcome with the First IVF/ICSI Cycle: A Randomized Clinical Trial.

PURPOSE: To investigate whether progestin-primed ovarian stimulation (PPOS) can be an alternative as gonadotrophin-releasing hormone agonist (GnRHa) long protocol for infertile women with normal ovarian reserve during IVF/ICSI. METHODS: A prospective randomized controlled trial (RCT) including 257 patients was conducted between 1 August 2017 to 1 January 2018. Computerized randomization was performed to assign participants into two treatment groups at a 1:1 ratio: PPOS (130 patients) or GnRHa long protocol (127 patients) followed by their first IVF/ICSI with fresh/frozen embryo transfer. The primary outcome was the number of oocytes retrieved. Patients with normal ovarian reserve undergoing their first IVF/ICSI procedure were included. The embryological and clinical outcomes were measured. Only the first embryo transfer cycle was followed-up. RESULTS: Basic characteristics such as infertility duration, age, and body mass index (BMI) were comparable in both groups. No significant difference was found in the number (mean ± SD) oocytes retrieved [11.8 ± 6.5 for PPOS vs 11.3 ± 5.6 for GnRHa long protocol] or viable embryos [4.5 ± 3.0 for PPOS vs 4.2 ± 2.9 for GnRHa long protocol] between the groups. No patient from either group experienced a premature LH surge during the whole process of ovarian stimulation. Besides, there was no moderate or severe ovarian hyperstimulation syndrome during the ovarian stimulation in PPOS group while three patients suffered it in the GnRHa long protocol group. There was no significant difference in the clinical pregnancy rate of the first embryos transfer cycle between the two groups. CONCLUSION: PPOS in combination with embryo cryopreservation as an ovarian stimulation regimen was as effective as GnRHa long protocol during controlled ovarian stimulation (COH) under different endocrinal mechanisms. It can also achieve comparable embryological and clinical outcomes while reducing the incidence of moderate and severe ovarian hyperstimulation syndrome (OHSS) and HMG dosage. It can be an alternative of the treatments for infertile patients with normal ovarian reserve undergoing IVF as well as traditional protocols. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17012089. TRIAL REGISTRATION DATE: Chictr.org.cn: 23 July 2017. DATE OF FIRST PATIENT'S ENROLLMENT: 1 August 2017.

Effect of body mass index on pregnancy outcomes with the freeze-all strategy in women with polycystic ovarian syndrome.

OBJECTIVE: To investigate the effects of body mass index (BMI) on assisted reproductive outcomes with the freeze-all strategy for patients with polycystic ovary syndrome (PCOS). DESIGN: Retrospective cohort study. SETTING: Tertiary care academic medical center. PATIENT(S): A total of 3,079 women with PCOS across different BMIs at our institution from January 2015 to May 2017 were stratified into cohorts. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate, early miscarriage rate, and live birth rate. RESULT(S): The live birth rate was most favorable in underweight (BMI < 18.5 kg/m2) and normal weight cohorts (18.5 ≤ BMI < 25 kg/m2) and progressively decreased as BMI increased. Moreover, the obese cohort (BMI ≥ 30 kg/m2) of patients with PCOS who had frozen ET cycles had a relatively high early miscarriage rate. CONCLUSION(S): The live birth rates are highest in underweight and normal weight patients with PCOS undergoing IVF with the freeze-all strategy. Furthermore, there is a progressive and statistically significant decrease in the live birth rate and an increase in the miscarriage rate in obese patients with PCOS.

miR­107­5p promotes tumor proliferation and invasion by targeting estrogen receptor­α in endometrial carcinoma.

The aberrant expression of miR107­5p is closely related to the development of several types of human cancers. However, the role of miR­107­5p in endometrial carcinoma (EC) has not been fully confirmed. In the present study, we aimed to explore the function of miR­107­5p in EC carcinogenesis. EC samples and normal endometrial tissues were obtained by laser capture microdissection. It was determined that the expression of miR­107­5p in EC was significantly higher than that in normal endometrium, and higher miR­107­5p expression was related to advanced FIGO stages, lymph node metastasis and myometrial invasion in EC patients. Blocking miR­107­5p significantly inhibited cell proliferation, migration and invasion of EC cells in vitro and in vivo. The results of bioinformatic algorithms and luciferase reporter assays revealed that estrogen receptor α (ERα) was a direct target of miR­107­5p. miR­107­5p downregulated the expression of ERα mRNA and protein. In conclusion, our results highlighted that miR­107­5p is a novel prognostic factor that targets ERα to promote tumor proliferation and invasion of EC.

Ideal embryo transfer position and endometrial thickness in IVF embryo transfer treatment.

OBJECTIVE: To establish an ideal transfer strategy by investigating the relationships among embryo transfer (ET) depth, endometrial thickness, and subsequent in vitro fertilization treatment clinical pregnancy outcomes. METHODS: In the present retrospective analysis, data from in vitro fertilization-ET treatment cycles conducted at a fertility center in Shanghai, China, between October 2014 and March 2015 were analyzed. Women were divided into groups 1-4 according to transfer depth (<10; 10-15, 15-20, and >20 mm, respectively), as measured by air bubbles. Additionally, 391 women were divided into groups A-C according to endometrial thickness (<7, 1-12, and >12 mm, respectively). Clinical pregnancy outcomes were assessed by group. RESULTS: Data from 501 cycles were included. Clinical pregnancy and live delivery rates were significantly higher in group 2 (P=0.009 and P=0.002, respectively) and group 3 (P=0.008 and P=0.001, respectively) than in group 4. Among the 394 patients with endometrial thickness data available, clinical pregnancy and live delivery rates were higher in group B (P=0.028 and P=0.015, respectively) and group (P=0.013 and P=0.013, respectively) than in group A. CONCLUSION: Correct transfer depth and endometrial thickness can increase the rates of clinical pregnancy, implantation, and live delivery. Placing the embryos at 10-20 mm from the fundus and at an endometrial thickness of more than 7 mm is recommended for optimal clinical pregnancy outcomes.

KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1.

Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity.

Twist induces epithelial-mesenchymal transition in cervical carcinogenesis by regulating the TGF-ß/Smad3 signaling pathway.

Epithelial-mesenchymal transition (EMT) is associated with the metastasis and poor prognosis of cervical cancer. However, the underlying mechanisms are poorly defined. In the present study, we investigated whether Twist plays a direct role in human cervical cancer using immunohistochemical and western blot analyses. Immunohistochemical analysis revealed that Twist is highly expressed in cervical cancer, which correlates with poor tumor pathological differentiation or lymph node metastasis (P<0.05). Depletion of Twist by stable shRNA-mediated knockdown decreased the migratory ability of cancer cell lines in vitro. Suppression or overexpression of Twist also resulted in an altered expression of the molecular mediators of EMT. Furthermore, exogenous TGF-ß promoted EMT by upregulating the expression of Twist through the TGF-ß/Smad3 pathway, and this effect was eliminated by Twist depletion in cancer cells as demonstrated in the in vitro study. The use of in vivo models revealed a decreased tumor proliferation potential in Twist-depleted cancer cells. The results suggested a novel function for Twist in the promotion of EMT via TGF-ß/Smad3 signaling pathway. Thus, Twist constitutes a potential therapeutic target in human cervical cancer.

Suppression of the epithelial-mesenchymal transition by SHARP1 is linked to the NOTCH1 signaling pathway in metastasis of endometrial cancer.

BACKGROUND: Mechanisms governing the metastasis of endometrial cancer (EC) are poorly defined. Recent data support a role for Enhancer-of-split and hairy-related protein 1 (SHARP1), a basic helix-loop-helix transcription repressor, in regulating invasiveness and angiogenesis of several human cancers. However, the role of SHARP1 in metastasis of EC remains unclear. METHODS: Human EC cell lines (Ishikawa and HEC-1B) were used. SHARP1 was upregulated by lentivirus transduction, while intracellular domain of NOTCH1 (ICN) were upregulated by transient transfection with plasmids. Effects of SHARP1 on cell migration and invasion were evaluated by wound healing assay and transwell invasion assay. Experimental metastasis assay were performed in nude mice. Effects of SHAPR1 on protein levels of target genes were detected by western blotting. Furthermore, the association between SHARP1 and the NOTCH1/EMT pathway was further verified in EC tissue specimens by immunohistochemical analysis. RESULTS: Overexpression of SHARP1 in EC cells inhibited cell migration, invasion, and metastasis. Exogenous SHARP1 overexpression affected the proteins levels of genes involved in EMT process and NOTCH1 signaling pathway. Upregulation of ICN in SHARP1-overexpressing Ishikawa cells induced cell migration and an EMT phenotype. Additionally, immunohistochemical analysis demonstrated that SHARP1 protein levels were lower in metastatic EC than in primary tumors, and statistical analysis revealed correlations between levels of SHARP1 and markers of EMT and NOTCH1 signaling pathway in human EC tissue specimen. CONCLUSIONS: This work supports a role for SHARP1 in suppressing EMT and metastasis in EC by attenuating NOTCH1 signaling. Therefore, SHARP1 may be a novel marker for lymphatic metastasis in EC patients.

SHARP1 suppresses angiogenesis of endometrial cancer by decreasing hypoxia-inducible factor-1α level.

Recent data support a role for SHARP1, a basic helix-loop-helix transcription repressor, in the regulation of malignant cell behavior in several human cancers. However, the expression and role of SHARP1 during the development of endometrial cancer (EC) remain unclear. Here we show that upregulation of SHARP1 suppressed tumor angiogenesis by decreasing hypoxia-inducible factor-1α (HIF-1α), inhibited cell viability and tumor growth in EC. Immunohistochemical staining showed that the expression of SHARP1 was negatively correlated with tumor stage, histological grade, myometrial invasion, lymph node metastasis, blood vessel permeation in the myometrium and HIF-1α expression. Mechanistic studies showed that SHARP1 interacted with HIF-1α physically, and the protein level of HIF-1α and the mRNA level of its target genes (VEGFA, ANGPTL4 and CA9) were decreased by SHARP1 under hypoxia. Upregulation of SHARP1 in EC impeded hypoxia-induced angiogenesis by reducing VEGF secretion. Immunohistochemical analysis verified a correlation between decreased SHARP1 expression and increased microvessel density in EC tissues. Additionally, SHARP1 inhibited cell viability in EC cell lines. Overexpression of SHARP1 in vivo inhibited tumor growth and angiogenesis, and decreased HIF-1α expression. In this study, we established SHARP1 as a novel tumor suppressor of EC and shed light on the mechanisms by how SHARP1 inhibited EC progression. Therefore, SHARP1 may be a valuable prognostic biomarker for EC progression and shows promise as a new potential target for antiangiogenic therapeutics in human EC.

FOXA1 promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer.

BACKGROUND: Increasing evidence suggests that forkhead box A1 (FOXA1) is frequently dysregulated in many types of human cancers. However, the exact function and mechanism of FOXA1 in human endometrial cancer (EC) remains unclear. METHODS: FOXA1 expression, androgen receptor (AR) expression, and the relationships of these two markers with clinicopathological factors were determined by immunohistochemistry analysis. FOXA1 and AR were up-regulated by transient transfection with plasmids, and were down-regulated by transfection with siRNA or short hairpin RNA (shRNA). The effects of FOXA1 depletion and FOXA1 overexpression on AR-mediated transcription as well as Notch pathway and their impact on EC cell proliferation were examined by qRT-PCR, western blotting, co-immunoprecipitation, ChIP-PCR, MTT, colony-formation, and xenograft tumor-formation assays. RESULTS: We found that the expression of FOXA1 and AR in ECs was significantly higher than that in a typical hyperplasia and normal tissues. FOXA1 expression was significantly correlated with AR expression in clinical tissues. High FOXA1 levels positively correlated with pathological grade and depth of myometrial invasion in EC. High AR levels also positively correlated with pathological grade in EC. Moreover, the expression of XBP1, MYC, ZBTB16, and UHRF1, which are downstream targets of AR, was promoted by FOXA1 up-regulation or inhibited by FOXA1 down-regulation. Co-immunoprecipitation showed that FOXA1 interacted with AR in EC cells. ChIP-PCR assays showed that FOXA1 and AR could directly bind to the promoter and enhancer regions upstream of MYC. Mechanistic investigation revealed that over-expression of Notch1 and Hes1 proteins by FOXA1 could be reversed by AR depletion. In addition, we showed that down-regulation of AR attenuated FOXA1-up-regulated cell proliferation. However, AR didn't influence the promotion effect of FOXA1 on cell migration and invasion. In vivo xenograft model, FOXA1 knockdown reduced the rate of tumor growth. CONCLUSIONS: These results suggest that FOXA1 promotes cell proliferation by AR and activates Notch pathway. It indicated that FOXA1 and AR may serve as potential gene therapy in EC.

Forkhead-box A1 suppresses the progression of endometrial cancer via crosstalk with estrogen receptor α.

Mechanisms governing the function of Forkhead-box A1 (FOXA1), a member of the FOX class of transcription factors, have been extensively studied. However, little is known about the activities and expression pattern of FOXA1 in endometrial cancer (EC). In the present study, we investigated the level of FOXA1 in multiple human EC cell lines and clinical samples by immunohistochemistry, qRT-PCR and Western blot analysis. FOXA1 overexpression was observed in estrogen receptor (ER)α-positive EC cell lines (P=0.0048). In endometrial tissues, FOXA1 was significantly upregulated in both normal endometrium and well-differentiated endometrial cancer tissues (P<0.001). Functional analyses of FOXA1 were evaluated by MTT, plate colony formation and Transwell assay. The results revealed that forced expression of FOXA1 inhibited EC cell proliferation, whereas FOXA1 depletion promoted cell viability and was associated with tumorigenesis. The nude mouse tumor xenograft assay also confirmed that ablation of FOXA1 expression promoted cell proliferation. Furthermore, we found that knockdown of FOXA1 decreased the expression of ERα, and FOXA1 interacted with this receptor in the EC cell lines. Collectively, these experiments suggest that FOXA1 is a tumor suppressor in EC and has a possible interaction with ERα.

A TrkB-STAT3-miR-204-5p regulatory circuitry controls proliferation and invasion of endometrial carcinoma cells.

BACKGROUND: We previously identified TrkB as an oncogene involved in promoting metastasis in endometrial carcinoma (EC). Here, we sought to delineate the effect of changes in TrkB expression on the global profile of microRNAs (miRNAs) in EC cells and further investigated the correlation between the expression of certain miRNA and TrkB in the clinicopathologic characteristics of EC patients. METHODS AND RESULTS: Using quantitative reverse transcription-PCR (qRT-PCR), we found that expression of TrkB mRNA has no significant difference in transcript levels between normal endometrium and EC cells captured by laser capture microdissection, while immunohistochemistry results demonstrated a markedly higher expression of TrkB protein in EC tissues. The microRNA array showed that ectopic overexpression and knockdown of TrkB expression caused global changes in miRNA expression in EC cells. qRT-PCR results showed that elevated TrkB repressed miR-204-5p expression in EC cells. Furthermore, immunoblotting assays revealed that TrkB overexpression in IshikawaTrkB cells noticeably increased JAK2 and STAT3 phosphorylation, which, however, was aborted by TrkB knockdown in HEC-1BshTrkB cells. Moreover, ChIP assays showed that phospho-STAT3 could directly bind to STAT3-binding sites near the TRPM3 promoter region upstream of miR-204-5p. Interestingly, using bioinformatics analysis and luciferase assays, we identified TrkB was a novel target of miR-204-5p. Functionally, the MTT assays, clonogenic and Transwell assays showed that miR-204-5p significantly suppressed the clonogenic growth, migration and invasion of EC cells. Furthermore, miR-204-5p also inhibited the growth of tumor xenografts bearing human EC cells. Importantly, we found lower miR-204-5p expression was associated with advanced FIGO stages, lymph node metastasis and probably a lower chance for survival in EC patients. CONCLUSIONS: This study uncovers a new regulatory loop involving TrkB/miR-204-5p that is critical to the tumorigenesis of EC and proposes that reestablishment of miR-204-5p expression could be explored as a potential new therapeutic target for this disease.