Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

Lanostane triterpenoids with anti-proliferative and PTP1B/α-glucosidase inhibitory activities from the fruiting bodies of Ganoderma calidophilum.

Twelve previously undescribed and four known lanostane triterpenoids were isolated from the fruiting bodies of Ganoderma calidophilum. The structures of undescribed compounds, ganodecalones H-S (1-12), were elucidated by extensive spectroscopic analysis as well as ECD and NMR calculations. Compound 4 showed significant inhibitory activity against human leukaemia cell line K562, gastric cancer cell line SGC-7901, and cervical cancer cell line HeLa with IC50 values of 13.10 ± 0.19, 17.26 ± 4.75, and 4.36 ± 0.58 µM, respectively. Compound 16 exhibited inhibitory potency against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase with IC50 values of 30.2 ± 0.13 µM and 120.6 ± 0.14 µM, respectively. The binding sites and interactions of 16 with PTP1B and α-glucosidase were revealed using molecular docking simulations.

The role of B3GNT3 as an oncogene in the growth, invasion and migration of esophageal cancer cells.

PURPOSE: To investigate the role and mechanism of ß1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) in esophageal cancer (ESCA). METHODS: The starBase database was used to evaluate the expression of B3GNT3. B3GNT3 function was measured using KYSE-30 and KYSE-410 cells of esophageal squamous cell carcinoma (ESCC) cell lines. The mRNA levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8, clone formation assay and transwell assay were used to detect the changes of proliferation, invasion and migration. RESULTS: B3GNT3 expression was higher in ESCA tissues than in normal tissues. The overall survival rate of ESCA patients with high B3GNT3 expression was lower than that of ESCA patients with low B3GNT3 expression. In vitro functional experiments showed that the proliferation ability, migration and invasion ability of KYSE-30 and KYSE-410 cells with B3GNT3 interference were lower than those of the control, and the overexpression of B3GNT3 had the opposite effect. After silencing B3GNT3 expression in ESCC cell lines, the growth of both cell lines was inhibited and the invasiveness was decreased. Knockdown of B3GNT3 reduced the growth rate and Ki-67 expression level. CONCLUSIONS: B3GNT3, as an oncogene, may promote the growth, invasion and migration of ESCC cell.

The role of B3GNT3 as an oncogene in the growth, invasion and migration of esophageal cancer cells

Purpose: To investigate the role and mechanism of ß1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) in esophageal cancer (ESCA). Methods: The starBase database was used to evaluate the expression of B3GNT3. B3GNT3 function was measured using KYSE-30 and KYSE-410 cells of esophageal squamous cell carcinoma (ESCC) cell lines. The mRNA levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8, clone formation assay and transwell assay were used to detect the changes of proliferation, invasion and migration. Results: B3GNT3 expression was higher in ESCA tissues than in normal tissues. The overall survival rate of ESCA patients with high B3GNT3 expression was lower than that of ESCA patients with low B3GNT3 expression. In vitro functional experiments showed that the proliferation ability, migration and invasion ability of KYSE-30 and KYSE-410 cells with B3GNT3 interference were lower than those of the control, and the overexpression of B3GNT3 had the opposite effect. After silencing B3GNT3 expression in ESCC cell lines, the growth of both cell lines was inhibited and the invasiveness was decreased. Knockdown of B3GNT3 reduced the growth rate and Ki-67 expression level. Conclusion: B3GNT3, as an oncogene, may promote the growth, invasion and migration of ESCC cell.

Exercise training modalities in patients with lung cancer: a protocol for systematic review and network meta-analysis.

INTRODUCTION: Lung cancer is a common malignancy and a major cause of cancer-related deaths worldwide, ranking high in terms of morbidity and prevalence. Exercise is a well-established recovery aid for many chronic respiratory conditions and lung cancer. However, it is difficult to determine the superiority of different exercise training modalities using randomised controlled trials (RCTs) or pairwise meta-analyses. Our Bayesian network meta-analysis (NMA) aimed to compare the impact of different perioperative exercise training modalities on lung function, exercise capacity, adverse events, health-related quality of life and mortality in patients undergoing lung cancer surgery, including preoperative and postoperative patients. METHODS AND ANALYSIS: We will perform a comprehensive literature search using PubMed, EMBASE, Cochrane Library and Web of Science, from inception to May 2022, to identify studies that potentially provide data regarding exercise training modalities for patients with lung cancer. We will assess the risk of bias according to the Cochrane risk-of-bias tool and certainty of evidence for the main outcomes using the Grading of Recommendations Assessment, Development and Evaluation framework. Pairwise meta-analyses will be conducted using a random effects model and Stata software, and the NMA will be analysed using R software. ETHICS AND DISSEMINATION: Ethical approval and patient consent were not required because this study was a meta-analysis of published RCTs. The results of this study are submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42021278923.

A modified method for Billroth-II gastrojejunostomy after laparoscopy-assisted distal gastrectomy.

Background: There are many types of gastrojejunostomy reconstruction after laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer, each of which has merits and demerits. This study introduced a novel method (called pant-shaped anastomosis) involving the construction of a side-to-side anastomosis between the afferent loop and efferent loop at the site of gastrojejunal anastomosis using a linear stapler. The results of applying pant-shaped anastomosis to LADG were also analyzed. Methods: The clinical data of 96 patients who underwent LADG with pant-shaped anastomosis between June 2018 and June 2020 at The First Affiliated Hospital of Wannan Medical College (Wuhu City, China) were analyzed retrospectively. Results: All procedures were successfully completed without conversion to open laparotomy. An average pant-shaped anastomosis took 22 min to construct and had a mean incision length of 5.3 cm. The mean time to postoperative first flatus was 3.5 days. The mean time to intake of an oral semiliquid diet was 5.5 days. The average postoperative hospital stay was 8.2 days. No patient developed extraluminal bleeding, intraluminal bleeding, anastomosis leakage, afferent obstruction, internal herniation or pancreatitis. The proportion of patients who experienced significant reflux was 10.1% (Visick III-IV). In total, 62.6% of patients exhibited endoscopic reflux gastritis of grade 1 or less. Conclusions: Pant-shaped anastomosis is a safe and simple procedure. It is a feasible option to reduce afferent obstruction after LADG in patients with distal gastric cancer.

Manganese Phosphate-Doxorubicin-Based Nanomedicines Using Mimetic Mineralization for Cancer Chemotherapy.

Inorganic nanomaterials showed great potential as drug carriers for chemotherapeutics molecules due to their biocompatible physical and chemical properties. A manganese-based inorganic nanomaterial manganese phosphate (MnP) had become a new drug carrier in cancer therapy. However, the approach for manganese phosphate preparation and drug integration is still confined in complex methods. Inspired by mimetic mineralization, we proposed a "one-step" method for the preparation of manganese phosphate-doxorubicin (DOX) nanomedicines (MnP-DOX) by manganese ion and DOX complexation. The structural characterization results revealed that the prepared MnP-DOX nanocomplexes were homogeneous with controlled sizes and shapes. More importantly, the MnP-DOX nanocomposites could significantly induce cancer inhibition in vitro and in vivo. The results indicated that the drug molecules were integrated into MnP nanocarriers by mimetic mineralization, which not only prevented the premature release of the drug but also reduced excessive modification. Moreover, the designed MnP-DOX complex showed high loading efficacy and pH-dependent degradation leading to drug release, achieving high efficiency for cancer chemotherapy in vitro and in vivo via a facile process. These achievements presented an approach to construct the manganese phosphate-based chemotherapy nanomedicines by mimetic mineralization for cancer therapy.

Primary spindle cell sarcoma of the seminal vesicle: A case report and literature review.

We report a case of primary seminal vesicle spindle cell sarcoma of a 57-year-old man who underwent multiple surgical treatment. The first diagnosis of a local hospital was a right seminal vesicle cyst, so only laparoscopic decompression was performed. Postoperatively, the patient gradually developed lower abdominal discomfort, frequent and urgent urination, dysuria and constipation. Digital rectal examination palpated a heterogeneous mass. Magnetic resonance imaging showed a multilocular cystic mass of about 4.5 cm in diameter in the right seminal vesicle, which was diagnosed as a recurrent cyst. The patient underwent a second operation in our hospital, but the tumour could not be completely removed because of severe peripheral adhesions. The postoperative pathological diagnosis was seminal vesicle cystadenoma with spindle cell sarcoma. One month later, a computed tomography scan performed at another hospital showed that the mass had invaded the bladder and sigmoid colon. The pathological diagnosis of re-examination was spindle cell liposarcoma. After neoadjuvant chemotherapy, extended resection of the tumour was performed, and adjuvant chemotherapy was continued after surgery. The total duration of follow-up was 19 months and 3 months after the third surgery. The patient survived with no recurrence or metastasis.

A Modified Anastomosis Technique for Esophagojejunostomy after Laparoscopy-Assisted Total Gastrectomy: A Single Team Preliminary Experience.

RESULTS: There were no significant differences between the cRY group and pRY group regarding age, sex, BMI, neoadjuvant therapy, preoperative comorbidities, history of laparotomy, ASA score, tumor location, pathological stage, total operative time, incision length, blood loss, time-to-first flatus, time-to-first soft diet, and postoperative hospital stays. The proportions of patients who received a 21 mm stapler were higher in the cRY group (7/44) than that in the pRY group (0/68) (P = 0.003). 7 anastomotic complications were reported (6 in the cRY group versus 1 in pRY group; P = 0.028) of which five (83.3%) in the cRY were anastomotic stenosis versus none in the pRY group (P = 0.044). CONCLUSIONS: The application of pant-shaped anastomosis for esophagojejunostomy after LTG is a safe and feasible procedure and has an advantage when the jejunum diameter is small.

The clinical effectiveness of establishing a proximal jejunum pouch after laparoscopic total gastrectomy: A propensity score-based analysis.

BACKGROUND: In this study, we propose an improved Roux-en-Y (RY) surgical method by constructing a proximal jejunum pouch (PP-RY). Postoperative results were evaluated among patients with gastric cancer who underwent PP-RY and standard RY anastomosis. METHODS: The clinical data of patients with gastric cancer who underwent laparoscopic total gastrectomy (LTG) in our center from May 2019 to May 2020 were collected retrospectively. We compared the short-term results of patients in the PP-RY and RY groups using 1:1 propensity score matching (PSM). RESULTS: A total of 317 patients were selected, including those who received RY (n = 249) or PP-RY (n = 68) after LTG. After PSM, both groups had a sample size of 68. During the one-year follow-up period, the incidences of postoperative dumping syndrome (5.6%) and reflux esophagitis (14.8%) were significantly lower in the PP-RY group (P = 0.001 and P = 0.010, respectively). Weight loss (6.5 ± 2.0 kg) and albumin decrease (0.2 ± 0.1 g/dl) were significantly lower (P = 0.038 and P < 0.001, respectively), and the prognostic nutritional index (PNI) was significantly higher in the PP-RY group (P = 0.009). In the QLQ-C30 scale, the degree of anorexia in the PP-RY group was significantly lower than that in the RY group (P＜0.05). In the QLQ-STO22 scale, chest and abdomen pain, dietary restriction, and anxiety were significantly lower in the PP-RY group (all P＜0.05). CONCLUSION: PP-RY can lead to obvious improvements in nutritional status, reduce short-term complications, and improve quality of life (QoL) for patients after LTG.

The Oncogenic Role of APC/C Activator Protein Cdc20 by an Integrated Pan-Cancer Analysis in Human Tumors.

The landscape of CDC20 gene expression and its biological impacts across different types of cancers remains largely unknown. Here, a pan-cancer analysis was performed to analyze the role of Cdc20 in various human cancers. Our results indicated that the expression levels of the CDC20 gene were significantly elevated in bladder cancer, breast cancer, colon cancer, rectum cancer, stomach cancer, esophageal cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, prostate cancer, pancreatic cancer, and uterine cancer. In addition, the expression of CDC20 was significantly and positively correlated with the increase of clinical stages in multiple cancer types, including breast cancer, kidney cancer, and lung cancer, et al. Among 33 cancer subtypes in the TCGA dataset, the high expression of CDC20 was correlated with poor prognosis in 10 cancer types. Furthermore, the abundance of phosphorylated Cdc20 in the primary tumor was elevated and correlated with increased tumor grade. Next, we sought to elucidate the oncogenic role by analyzing its association with immune infiltration. For most cancer types, the CDC20 expression was positively correlated with the infiltration of cancer-associated fibroblasts and myeloid-derived suppressor cells. To further understand its functional activity, we explored the classic Cdc20 downstream substrates, which were found to be mutually exclusive with the expression of Cdc20. Moreover, the pan-cancer analysis of the molecular function of Cdc20 indicated that BUB1, CCNA2, CCNB1, CDK1, MAD2L1, and PLK1 might play a critical role in interaction with Cdc20. The abundance of Cdc20 was further validated at transcriptional and translational levels with a publicly available dataset and clinical tumor tissues. The knockdown of Cdc20 dramatically inhibited tumor growth both in vivo and in vitro. Therefore, our studies delineated the oncogenic role of CDC20 and its prognostic significance at the pan-cancer level and proved its functional activity in Cdc20 high expression cancer types. Our studies will merits further molecular assays to understand the potential role of Cdc20 in tumorigenesis and provide the rationale for developing novel therapeutic strategies.

ßKlotho Inhibits Cell Proliferation by Downregulating ELK4 and Predicts Favorable Prognosis in Prostate Cancer.

OBJECTIVE: Prostate cancer (PCa) ranks as the second common malignancy in males worldwide. Although conspicuous progressions in diagnosis and treatment have been achieved in the past decades, the prognosis expectation of PCa remains unsatisfied yet. To improve the prognosis prediction of PCa, more specific biomarkers are needed. In this retrospective research, we focused on ßKlotho and ETS-like transcription factor 4 (ELK4), aiming to identify potential prognostic biomarkers for PCa. METHODS: Western blotting was used to determine the expression of ßKlotho, ELK4, and PARP in C4-2B and PC3 PCa cell lines. CCK-8 assay and colony formation assay were applied to examine the roles of ßKlotho and ELK4 in the proliferation of PCa cells. The expression of ßKlotho and ELK4 in PCa tissue samples was determined by immunochemistry. Pearson's χ2 test and Fisher's exact test were performed to investigate the associations among ßKlotho, ELK4 and various clinical factors. Kaplan-Meier curves and Cox regression model were established to reveal the correlation among ßKlotho, ELK4 expression and the prognosis of patients. RESULTS: ßKlotho overexpression down-regulated the ELK4 expression, induced apoptosis and inhibited cell proliferation in both C4-2B and PC3 cells, which were reversed by ELK4 overexpression. ßKlotho expression in PCa tissue samples had negative correlation with the ELK4 expression, and higher ßKlotho expression was associated with lower Gleason score, absent distant metastasis and lower prostate-specific antigen (PSA) level. On the contrast, higher ELK4 expression was correlated with distant metastasis and higher PSA level. Moreover, ßKlotho and ELK4 were both recognized as independent factors for the prognosis of patients with PCa. CONCLUSION: ßKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both ßKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.

Multivalent effects of heptamannosylated ß-cyclodextrins on macrophage polarization to accelerate wound healing.

Macrophages have high plasticity and heterogeneity, and can suppress or mediate inflammation, depending on their cytokine secretion and phenotype. Regulating macrophage polarization into its M2 phenotype has a remarkable effect on inflammatory inhibition, inducing the regeneration of injured tissues. Here, we synthesized two heptamannosylated ß-cyclodextrin derivatives (CD-Man7 and C3-CD-Man7) and demonstrated that their multivalent mannose ligands could induce M2 macrophage polarization to accelerate wound healing. Unlike hydrophilic CD-Man7, amphiphilic C3-CD-Man7 can self-assemble to form nanoparticles (CD-Man-NPs) in aqueous solution. Further, in vitro results confirmed that multivalent mannose ligands of either CD-Man7 or CD-Man-NPs stimulated RAW264.7 macrophages to differentiate into the M2 phenotype, which promoted fibroblast migration via a paracrine mechanism. In vivo results confirmed that both CD-Man7 and CD-Man-NPs reduced the inflammatory response in wound tissue and accelerated wound healing. The present study demonstrates multivalent effects of CD-Man7 and CD-Man-NPs on M2 macrophage polarization, indicating the therapeutic potential of these ß-cyclodextrin glycoconjugates in the treatment of inflammatory diseases and wound healing.

Synergistic photodynamic and photothermal therapy of BODIPY-conjugated hyaluronic acid nanoparticles.

The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) has emerged as a promising strategy for complete tumor ablation therapy. Herein, a boron dipyrromethene (BODIPY)-conjugated hyaluronic acid polymer that can self-assemble to form the nanoparticles (BODIPY-HA NPs) was prepared for combined cancer PDT and PTT. The fluorescence emission and reactive oxygen species (ROS) generation of BODIPY-HA NPs were inhibited because of the π-π stacking behavior of BODIPY, resulting in photothermal effect under 808 nm light irradiation. Upon the internalization by cancer cells, the BODIPY-HA NPs could disassemble into BODIPY-HA molecules, with the recovery of the fluorescence and ROS generation for PDT. Importantly, in vitro results confirmed that combined PTT and PDT have exhibited better anticancer effect than PTT alone upon 808 nm laser irradiation. These results showed that the self-assembled BODIPY-HA NPs may be a promising nanomedicine for synergistic cancer PDT and PTT.

Inorganic material based macrophage regulation for cancer therapy: basic concepts and recent advances.

Macrophages with the M1 phenotype are a type of immune cell with exciting prospects for cancer therapy; however, when these macrophages infiltrate into tumours, many of them are induced by the tumour microenvironment to transform into the M2 type, which can enable tumour defence against external therapeutic strategies, assisting in tumour development. Macrophages have strong plasticity and functional heterogeneity, and their phenotypic transformation is complex and still poorly understood in relation to cancer therapy. Recent material advances in inorganic nanomaterials, especially inorganic elements in vivo, have accelerated the development of macrophage regulation-based cancer treatments. This review summarizes the basics of recent research on macrophage phenotype transformation and discusses the current challenges in macrophage type regulation. Then, the current achievements involving inorganic material-based macrophage regulation and the related anticancer effects of induced macrophages and their extracellular secretions are reviewed systematically. Importantly, inorganic nanomaterial-based macrophage phenotype regulation is flexible and can be adapted for different types of cancer therapies, presenting a possible novel approach for the generation of immune materials for cancer therapy.

Integrated Protein-Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in Hepatoblastoma.

Hepatoblastoma (HB) is the most common liver tumor in the pediatric population, with typically poor outcomes for advanced-stage or chemotherapy-refractory HB patients. The objective of this study was to identify genes involved in HB pathogenesis via microarray analysis and subsequent experimental validation. We identified 856 differentially expressed genes (DEGs) between HB and normal liver tissue based on two publicly available microarray datasets (GSE131329 and GSE75271) after data merging and batch effect correction. Protein-protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA) were conducted to explore HB-related critical modules and hub genes. Subsequently, Gene Ontology (GO) analysis was used to reveal critical biological functions in the initiation and progression of HB. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that genes involved in cell cycle phase transition and the PI3K/AKT signaling were associated with HB. The intersection of hub genes identified by both PPI and WGCNA analyses revealed five potential candidate genes. Based on receiver operating characteristic (ROC) curve analysis and reports in the literature, we selected CCNA2, CDK1, and CDC20 as key genes of interest to validate experimentally. CCNA2, CDK1, or CDC20 small interfering RNA (siRNA) knockdown inhibited aggressive biological properties of both HepG2 and HuH-6 cell lines in vitro. In conclusion, we identified CCNA2, CDK1, and CDC20 as new potential therapeutic biomarkers for HB, providing novel insights into important and viable targets in future HB treatment.

Biosilicified oncolytic adenovirus for cancer viral gene therapy.

Oncolytic adenoviruses (OAs) have shown great potential for cancer viral gene therapy in clinical studies. To date, clinical trials have shown that the curative efficacy of OAs is still limited by hepatic sequestration and preexisting neutralizing antibodies (nAbs), which decrease the accumulation of the OAs in tumors. Herein, with the biosilicification method, we encapsulated an OA encoding the anticancer gene Trail (OA-Trail) with silica, which significantly improved virus distribution and tumor inhibition. In vitro and in vivo results indicated that compared with the native OA, biosilicified OA-Trail (OA-Trail@SiO2) showed significantly reduced viral clearance in the liver and evaded nAb degradation, inducing an efficacious anticancer effect under the premise of biocompatibility. These achievements present an alternative strategy involving biosilicification for enhanced OA-based cancer gene therapy.

Different levels of estradiol are correlated with sexual dysfunction in adult men.

Ejaculatory dysfunction, including premature ejaculation (PE) and delayed ejaculation (DE), as well as erectile dysfunction (ED), constitute the majority of male sexual dysfunction. Despite a fair amount of data on the role of hormones and erection and ejaculation, it is inconclusive due to controversy in the current literature. To explore the correlation of male sexual dysfunction with hormonal profile, 1,076 men between the ages of 19-60 years (mean: 32.12 years) were included in this retrospective case-control study; 507 were categorized as ED, PE and DE groups. Five hundred and sixty-nine men without sexual dysfunction were enrolled in the control group. The background characteristics and clinical features of the four groups were collected and analyzed. The estradiol value was significantly elevated in the ED group than the control group (109.44 ± 47.14 pmol/L vs. 91.88 ± 27.68 pmol/L; P < 0.001). Conversely, the DE group had significantly lower level of estradiol than control did (70.76 ± 27.20 pmol/L vs. 91.88 ± 27.68 pmol/L; P < 0.001). The PE group had similar level of estradiol (91.73 ± 31.57 pmol/L vs. 91.88 ± 27.68 pmol/L; P = 0.960) but significantly higher level of testosterone (17.23 ± 5.72 nmol/L vs. 15.31 ± 4.31 nmol/L; P < 0.001) compared with the control group. In conclusion, elevated serum testosterone concentration was an independent risk factor for PE. Besides, there was a progressively increasing graded-distribution of estradiol values from DE to PE and ED groups.