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Mounting evidence has demonstrated that a myriad of developmental signaling pathways, such as the Wnt, Notch, Hedgehog and Hippo, are frequently deregulated and play a critical role in regulating cancer stem cell (CSC) activity in human cancers, including gynecologic malignancies. In this review article, we describe an overview of various signaling pathways in human cancers. We further discuss the developmental roles how these pathways regulate CSCs from experimental evidences in gynecologic cancers. Moreover, we mention several compounds targeting CSCs in gynecologic cancers to enhance the treatment outcomes. Therefore, these signaling pathways might be the potential targets for developing targeted therapy in gynecologic cancers.

Exploiting a tissue diagnosis method to abstain the involuted operating and consume valuable reagents while realizing high-speed and inexpensive pathological grading technology to supply a better scheme for cancer therapy is a significant method of cancers detection. A promising immuno-fluorescence strategy was rationally designed and synthesized by loading ruthenium complex into cervical cancer-targeted DNA-cage, which was well used to realize high-speed and inexpensive diagnosis of clinical cervical cancer tumor tissues avoiding the traditional multi-stage process, thus demonstrating high application potential in clinical pathological grading and surgical judgment. Moreover, it has been finding that Apts-DNA@Ru can enrichment in the tumor region, interestingly, no enrichment in normal cervical cancer tissue. It has the potential to realize the integration of in vivo diagnose and further synchronous treatment in the near future. Thence, this study demonstrates a strategy for integration of cancer-targeted DNA-cage and fluorescent RuPOP as alternative IHC reagents for next-generation more rapid convenient cancer detection.

In the wireless charging process of electric vehicles, unmanned aerial vehicles (UAVs), inspection robots and other electrical equipment, coil misalignment is inevitable due to human factors, external factors such as airflow during landing and other positioning problems, which severely limits its application. Accurate localization of the receiver coil can effectively reduce or even avoid the misalignment, but the traditional localization techniques may not be suitable for the complex electromagnetic environment of wireless charging system. In this paper, a receiver localization method based on mutual inductance disturbance for wireless power transfer (WPT) system with a relay coil is proposed. This method can achieve two-dimensional (2-D) localization of the receiver coil, and it will be more effective for high-temperature superconducting (HTS) WPT system with larger transmission power. The simulation and experiment are carried out to locate the receiver coil, and the results verify the feasibility of the proposed method.

Cervical cancer is the most common gynecologic malignancy worldwide. Methyltransferase-like 3 (METTL3) is involved in tumorigenesis; however, it is unclear whether METTL3 plays a potential role in regulating cisplatin (DDP) resistance. Therefore, the role of METTL3 in the regulation of cisplatin sensitivity in cervical cancer cells was determined. Our immunohistochemistry (IHC) data showed that METTL3 was highly expressed in para-cancerous compared with cervical cancer tissues. Furthermore, METTL3 overexpression inhibited viability and increased cisplatin sensitivity of cervical cancer cells in vitro. Overexpression of METTL3 inhibited tumor growth in vivo. IHC results showed that the receptor for advanced glycation and products (RAGE) had higher expression levels in cervical cancer tissues. RAGE downregulation increased cell sensitivity to cisplatin treatment. Moreover, the combination of FPS-ZM1 with cisplatin was more effective in inhibiting cell viability as compared with FPS-ZM1 or cisplatin only. Additionally, METTL3 reduced RAGE expression in cervical cancer cells. Overexpression of METTL3 downregulated RAGE expression and caused more sensitivity to cisplatin treatment in the SiHa-DDP cell line. METTL3 inhibited cell viability and increased apoptosis as well as enhanced the sensitivity of cisplatin via downregulating RAGE expression in cervical cancer cells., Graphical abstract, METTL3 is a novel tumor suppressor in cervical cancer tumorigenesis and progression. METTL3 inhibits the growth of cervical cancer cells both in vitro and in vivo. Moreover, METTL3 suppresses the activity of RAGE, thus increasing the cisplatin sensitivity in cervical cancer.

Background: The x-ray repair cross-complementing (XRCC) family is essential in DNA repair processes. The predictive roles of XRCCs remain unclear in ovarian carcinomas. Therefore, detecting the relationship between XRCCs expression and ovarian carcinomas prognosis is increasingly pivotal. Methods: Using the "Kaplan-Meier (KM) plotter" database, progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the prognosis of XRCCs mRNA expression in ovarian carcinoma patients with clinical outcomes. Then, mRNA level and protein levels of XRCCs were assessed in normal ovarian cells and ovarian carcinoma cell lines by real-time qPCR, Western blotting and immunofluorescence analysis. Additionally, expression of the XRCCs protein in tissues from ovarian carcinomas and normal ovary was identified by immunohistochemical staining. Results: Higher mRNA levels of XRCC2 and XRCC9 predicted longer PFS and OS in all women with ovarian malignance, while elevated XRCC4 mRNA levels were linked to poor PFS and OS in all ovarian cancer patients. Elevated mRNA of XRCC2 was also correlated with better PFS in patients with serous ovarian carcinomas, and better PFS and OS in grade III and stage III+IV ovarian carcinomas patients. What's more, highly expressed levels of XRCC9 mRNA were also linked to favorable PFS and OS in patients with serous, grade III and stage III+IV ovarian carcinomas. Nevertheless, elevated mRNA expression of XRCC4 was linked to worse PFS and OS for patients with serous, grade III as well as all stages of ovarian malignance. Additionally, when compared to ovarian carcinoma cell lines, elevated mRNA and protein levels of XRCC2 and XRCC9 were detected in normal ovarian cells. Consistently, higher staining of XRCC2 and XRCC9 was also detected in normal ovarian cells than that in ovarian cancer cells. Then, higher staining levels of XRCC2 and XRCC9 were discovered in healthy control tissues than that in ovarian carcinoma tissues. Meanwhile, XRCC4 was identified to be overexpressed in tissues of ovarian malignance as compared to normal control tissues. However, XRCC4 mRNA and protein levels were lower in ovarian cancer cells than that in normal cell line. Conclusion: Elevated XRCC2 and XRCC9 expression levels were observed in normal ovarian cells and tissues than that in ovarian malignance cells and tissues, and exhibited better prognostic value especially in patients with serous, poor differentiated and late stage, suggesting that XRCC2 and XRCC9 may be potent prognostic markers in ovarian cancer patients and can guide personalized surveillance for ovarian malignance.

In addition to being suitable for the assessment of residual urine volume, the use of a portable bladder scanner can also assist medical staff in developing a reasonable urination plan. Portable scanners can help medical personnel to estimate the height and/or relaxation of the bladder neck for pelvic floor muscle training, assist in the efficacy evaluation of muscarinic antagonists in patients with neurogenic detrusor overactivity, and even determine whether the urine in the bladder of pediatric patients meets the criteria for catheterization to obtain urine samples. However, in the case described herein, we encountered abnormal deviation between the data measured by a portal bladder scanner and actual catheterization. The patient was a 65-year-old male suffering spinal nerve dysfunction due to tuberculous meningitis. He had functional dysuria and a history of liver cirrhosis, accompanied by a large amount of ascites. We therefore deduced that the deviation in the scanning data was attributable to the ascites. After the patient’s ascites had resolved, the residual urine volume obtained via scanning evaluation was comparable to that obtained through catheterization. Our case shows that in the event of abnormal deviation in portable bladder scanner measurements, clinical judgements should be made based on the patient’s condition rather than the scanning results alone.

Cervical cancer is a common female malignancy that is mainly caused by human papillomavirus (HPV) infection. However, the incidence of HPV-negative cervical cancer has shown an increasing trend in recent years. Because the mechanism of HPV-negative cervical cancer development is unclear, this study aims to find the pattern of differential gene expression in HPV-negative cervical cancer and verify the underlying potential mechanism. Differentially expressed genes were compared among HPV-positive cervical cancer, HPV-negative cervical cancer, and normal cervical tissues retrieved from TCGA. Subsequently, dysregulated differentially expressed genes specifically existed in HPV-negative cervical cancer tissues and HPV-negative cell lines were validated by qRT-PCR, western blotting, and immunohistochemical staining. We found seventeen highly expressed genes that were particularly associated with HPV-negative cervical cancer from analysis of TCGA database. Among the 17 novel genes, 7 genes (preferentially expressed antigen in melanoma [PRAME], HMGA2, ETS variant 4 [ETV4], MEX3A, TM7SF2, SLC19A1, and tweety-homologs 3 [TTYH3]) displayed significantly elevated expression in HPV-negative cervical cancer cells and HPV-negative cervical cancer tissues. Additionally, higher expression of MEX3A and TTYH3 was associated with a shorter overall survival of patients with HPV-negative cervical cancer. Our study implies that these seven genes are more likely to provide novel insights into the occurrence and progression of HPV-negative cervical cancer.

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but the outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signalling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and microRNA, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in the immune escape of cervical cancer through inhibition of host immune response. Creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for the therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PDL1/ PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

Objective: To define the alteration of tweety homolog (TTYH) expression in patients with ovarian carcinoma (OC) and its correlation to prognosis. Methods: Kaplan-Meier (KM) plotter was used to evaluate the association between TTYHs expression and clinical outcomes of OC patients. The distribution of 20-year overall survival (OS) and progression-free survival (PFS) was estimated using KM survival plots. The mRNA expression of TTYHs in OC and normal ovarian tissues was confirmed by the Oncomine database. Then, using immunohistochemistry assay, the expression of TTYH1 and TTYH3 proteins in serous OC and normal ovarian tissues was detected. In addition, the protein and mRNA levels of TTYH1 and TTYH3 in human OC cell lines ES-2, A2780 and SKOV3 and normal ovarian epithelial cell lines IOSE80 were assessed by western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: TTYH1 possessed meaningful significance in predicting better prognosis in the serous, advanced stage, and well-differentiated OC patients, while TTYH3 expression predicted worse prognosis in serous, late-stage, and poorly differentiated OC patients. High expression of TTYH1 displayed an association with favorable PFS in OC patients with TP53 mutation. However, enhanced TTYH3 was related to an adverse clinical outcome in TP53-mutated OC patients. In addition, TTYH1 was related to a better clinical outcome in OC patients with platinums-based chemotherapy, but only indicated improved overall survival in OC patients who received taxol or platin + taxol chemotherapy. The up-regulated expression of TTYH3 predicted worse survival in OC patients receiving platin, taxol, or platin + taxol chemotherapy regimen. The levels of TTYH3 mRNA and protein were higher in OC cells and tissues when compared to normal ovarian cells and tissues. Conclusions: TTYH3 was a potential predictor for poor clinical outcome in OC patients, particularly in patients with serous, late-stage, poorly differentiated, TP53-mutation or the patients treated with chemotherapy regimens (platin, taxol, or platin + taxol).

The role of infiltrating immune cells within the tumor microenvironment has received considerable attention, but their function in cervical cancer remains to be elucidated; thus, comprehensive evaluation of their predictive value is needed. Using cervical cancer samples from 406 patients, immune cell infiltration was evaluated via immunohistochemistry. CD3+, CD4+, CD8+, CD20+, CD57+, CD68+, and CD163+ cell infiltration was compared in samples from adjacent tissues and the tumor center. The associations between immune cell distributions in the tumor center, clinicopathological features, and prognosis were correlated among immune cell types. Using three immune features, an immune model was constructed based on a Cox regression analysis with the least absolute shrinkage and selection operator (lasso) penalty to derive immune risk scores. Immune cells that infiltrated the tumor center correlated with clinicopathological characteristics and prognosis. The immune risk scores were an independent prognostic indicator and were found to predict cervical cancer prognosis as well as the effects of chemoradiotherapy. We classified patients into either high- or low-risk subgroups (namely CD4+highCD163+highCD57+low and CD4+lowCD163+lowCD57+high, respectively) based on their immune scores. Significant differences were found in the 3-year overall survival of patients with high- and low-risk scores (83.0% vs. 96.6%; P < 0.001). High immune risk scores resulted in decreased overall survival for patients in stages IB1+IIA1, IB2+IIA2, and IIB-IV (P = 0.001, P = 0.008, and P = 0.044, respectively). Overall survival was significantly worse following chemoradiotherapy in high-scoring patients in stages IB1+IIA1 and IB2+IIA2 (P = 0.001 and P=0.008, respectively). Moreover, overall survival was significantly worse after radiotherapy or chemotherapy in high-scoring patients in stage IB1+IIA1 (P = 0.03). Our work reveals that the distribution of infiltrating immune cells affects their function in cervical cancer. Our tumor center-centric immune model effectively predicted survival, suggesting its potential use in identifying suitable candidates for chemoradiotherapy.

Uterine fibroids and thyroid nodules, both of which are crucially affected by estrogen, are common diseases among reproductive-age women. However, little attention has been paid to the association between the two diseases. This retrospective case-control study aimed to assess the relationships among thyroid nodules, thyroid function and uterine fibroids in China. We reviewed the electronic records of 853 reproductive-age women who attended health check-ups at the Second Affiliated Hospital of Wenzhou Medical University from July 1st, 2017, to June 30th, 2018. All subjects received transvaginal pelvic ultrasound, thyroid ultrasound, thyroid function, and other laboratory tests. We found that the prevalence of thyroid nodules in subjects with uterine fibroids was remarkably higher than that in subjects without fibroids. The proportion of thyroid nodules ≥1 cm in subjects with uterine fibroids was significantly higher than that in subjects without fibroids. Women with thyroid nodules had a higher proportion of multiple uterine fibroids than women without thyroid nodules. Among the parameters of thyroid function, the only statistically significant parameter was total triiodothyronine, i.e., women with uterine fibroids had lower total triiodothyronine levels than unaffected controls; however, the total triiodothyronine levels were within the normal ranges. Moreover, no significant difference was noted in thyroid hormone status between subjects with and without uterine fibroids. Our findings suggest that thyroid nodules are positively correlated with uterine fibroids among reproductive-age women in China. Further studies are needed to confirm this association and fully understand the common pathogenetic mechanism underlying the association between uterine fibroids and thyroid nodules.

Objectives Human papillomavirus (HPV) has been reported recently in surgical smoke generated by gynecological operations. The objective of this study was to investigate whether gynecologists who have performed electrosurgery including loop electrosurgical excision procedure (LEEP), are at risk of acquiring HPV DNA through surgical smoke. Methods A related questionnaire was designed and 700 gynecologist nasal swab samples were collected in 67 hospitals. In addition, the flow fluorescence hybridization technique was used to detect HPV DNA, and the Chi-square test was applied to analyze whether related risk factors including electrical surgery, were correlated with HPV infection in surgeons’ nasal epithelial cells. Results The HPV infection rate in the nasal epithelial cells of the participants who performed electrosurgery (8.96%, 42/469) or LEEP (10.11%, 36/356) was significantly higher than that in the remaining participants who did not perform electrosurgery (1.73%, 4/231) or LEEP (2.91%, 10/344), respectively. The most prevalent HPV genotype in the electrosurgery group was HPV16 (76.19%, 32/42). The HPV-positive rate was increased in the group that had a longer duration of electrosurgery (P = 0.016). Additionally, the HPV detection rate was significantly lower in electrosurgery operators who used surgical mask (7.64%, 33/432) than in those who did not use protective masks (24.32%, 9/37). Furthermore, the N95 mask (0%, 0/196) significantly reduced the risk for HPV infection compared to that with the general mask (13.98%, 33/236, P Conclusions Gynecologists who performed electrosurgery including LEEP were at risk of acquiring HPV infection. Surgical masks, especially the N95 mask, significantly decreased the hazard of HPV transmission from surgical smoke.

Purpose Although the mortality of elderly women with cervical cancer is high, their characteristics and prognosis have not attracted sufficient attention. This study aims to clarify the prognostic factors of cervical cancer patients aged ≥65. Patient and Methods The incidences and characteristics of patients diagnosed with cervical cancer (aged ≥65 and

Inhaled anesthetics are widely used for induction and maintenance of anesthesia during surgery, including isoflurane, sevoflurane, desflurane, haloflurane, nitrous oxide (N2O), enflurane and xenon. Nowadays, it is controversial whether inhaled anesthetics may influence the tumor progression, which urges us to describe the roles of different inhaled anesthetics in human cancers. In the review, the relationships among the diverse inhaled anesthetics and patient outcomes, immune response and cancer cell biology were discussed. Moreover, the mechanisms of various inhaled anesthetics in the promotion or inhibition of carcinogenesis were also reviewed. In summary, we concluded that several inhaled anesthetics have different immune functions, clinical outcomes and cancer cell biology, which could contribute to opening new avenues for selecting suitable inhaled anesthetics in cancer surgery.

Ovarian cancer is one of the most lethal gynecologic tumors in women and has a poor prognosis. The purpose of our study was to identify new prognostic markers in ovarian cancer. We examined the prognostic roles of mRNA expression of the chromobox (CBX) family in patients with ovarian cancer utilizing the Kaplan-Meier plotter database. The prognostic values and expression levels of CBX members associated with prognosis were further evaluated using KM plotter in diverse subgroups and immunohistochemistry (IHC) analysis in ovarian carcinoma. The results revealed that elevated CBX1-3 mRNA expression may predict poor overall survival (OS) and progression-free survival (PFS) outcomes in patients with ovarian cancer. Notably, in women with ovarian cancer, increased CBX1 mRNA expression was linked to a short OS in all stages and in the grade II and grade III subgroups. Additionally, CBX2 and CBX3 were strongly related to short OS in stage III+IV patients, and a link between high CBX3 mRNA expression and unfavorable OS in grade II patients was observed. High expression levels of CBX1 and CBX3 were significantly associated with chemotherapy resistance in ovarian cancer patients. IHC staining showed that the CBX1-3 proteins were upregulated in serous ovarian carcinoma tissues compared with normal ovarian tissues. Therefore, our results indicated that CBX1-3 could be attractive biomarkers for predicting poor prognosis of ovarian cancer.

Ovarian cancer ranks as the fifth most common cause of cancer-related death in females. The molecular mechanisms of ovarian carcinogenesis need to be explored in order to identify effective clinical therapies for ovarian cancer. Recently, multi-omics approaches have been applied to determine the mechanisms of ovarian oncogenesis at genomics (DNA), transcriptomics (RNA), proteomics (proteins), and metabolomics (metabolites) levels. Multi-omics approaches can identify some diagnostic and prognostic biomarkers and therapeutic targets for ovarian cancer, and these molecular signatures are beneficial for clarifying the development and progression of ovarian cancer. Moreover, the discovery of molecular signatures and targeted therapy strategies could noticeably improve the prognosis of ovarian cancer patients.

Purpose To investigate the role of IGF-1 signaling pathway in the treatment of uterine leiomyomas with mifepristone. Patients and methods From October 2015 to December 2018, 50 patients with uterine leiomyoma were included in this study. Overexpression or siRNA of IGF-1 in primary human uterine leiomyoma cells were treated with or without mifepristone. MTT was used to evaluate cell viability in assays of cell proliferation and cytotoxicity. IGF-1 expression in the cells was measured with real-time RT-PCR and Western blotting and manipulated with lentivirus ectopic overexpression or siRNA silencing. Results Inhibition of cell viability by mifepristone was found dependent on drug concentration and treatment time. IGF-1 and phosphorylation-ERK1/2 expression were decreased, while phosphorylation-AKT expression was increased after mifepristone treatment. IGF-1 significantly promoted cell growth, while IGF-1 knockdown and mifepristone showed synergistic inhibition effects on cell growth. The overexpression of IGF-1 reversed the inhibition of cell growth and ERK1/2 phosphorylation but showed no effect on AKT phosphorylation. Conclusion Our study for the first time demonstrated that IGF-1 signaling via ERK1/2 appears to be an important target of mifepristone in the treatment of uterine leiomyomas, which may provide a new approach to avoid leiomyoma re-growth after cessation of mifepristone.

Background This study aims to investigate the expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 in bulky cervical squamous carcinoma and its predictive role in cisplatin-based neoadjuvant chemotherapy. Methods Initially, the expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 protein was analyzed in 13 human cervical squamous cancer tissues and their paired adjacent non-cancerous tissues by western-blotting and immunohistochemistry. Then, correlation between the expression of thioredoxin 1, peroxiredoxin 1, peroxiredoxin 2 and responses to cisplatin-based neoadjuvant chemotherapy was analyzed in 35 paired tumor samples (pre- and post-chemotherapy) from bulky cervical squamous cancer patients by immunohistochemistry. Results A clinical response occurred in 48.6% (17/35) of patients, including 14.3% (5/35) with a complete response and 34.3% (12/35) with a partial response. The expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 was much higher in cervical squamous cancer tissues compared with paired adjacent non-cancerous tissues by western-blotting and immunohistochemistry. Additionally, the expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 was significantly up-regulated in post-chemotherapy tissues compared to pre-chemotherapy cervical cancer tissues. High levels of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 were associated with a poor chemotherapy response in cervical squamous cancer patients. Conclusions Thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 are frequently over-expressed in cervical squamous cancer. High expression levels of these proteins were related to a poor response to cisplatin-based neoadjuvant chemotherapy. The present study is the first report that thioredoxin peroxidase system may serve as a prediction of the responses to neoadjuvant chemotherapy in cervical squamous cancer.

Surgical smoke is the gaseous by-product produced by heat generating devices in various surgical operations including laser conization and loop electrosurgical procedures that often are performed by gynecologists. Surgical smoke contains chemicals, blood and tissue particles, bacteria, and viruses, which has been shown to exhibit potential risks for surgeons, nurses, anesthesiologists, and technicians in the operation room due to long term exposure of smoke. In this review, we describe the detailed information of the components of surgical smoke. Moreover, we highlight the effects of surgical smoke on carcinogenesis, mutagenesis, and infection in gynecologists. Furthermore, we discussed how to prevent the surgical smoke via using high-filtration masks and smoke evacuation systems as well as legal guidelines for protection measures among the gynecologists.

E-cadherin plays a pivotal role in cancer progression, including the epithelial-mesenchymal transition (EMT) process and tumor metastasis. Loss of E-cadherin contributes to enhanced invasion and metastasis in human cancers. Therefore, restoring E-cadherin could be a potential approach for cancer therapy. Multiple natural compounds have been shown to possess anti-tumor activities through the regulation of key molecules in signaling pathways, including E-cadherin. In this review, we describe the numerous compounds that restore the expression of E-cadherin in genital and urinary malignancies. We further discuss the potential anti-tumor molecular mechanisms of these agents as the activators of E-cadherin in genital and urinary cancers. Although these compounds exhibit their potential to inhibit the development and progression of cancers, there are several challenges to developing them as therapeutic drugs for cancer patients. Poor bioavailability in vivo is the main disadvantage of these compounds. Modification of compound structures has produced actual improvements in bioavailability. Nanoparticle-based delivery systems could be useful to deliver the agents to targeted organs. These compounds could be new promising therapeutic agents for the treatment of human genital and urinary cancers. Further investigations are required to determine the safety and side effects of natural compounds using animal models prior to clinical trials. Keywords: E-cadherin, EMT, invasion, cancer, natural agents, therapy

Objective: The purpose of this study was to explore whether human papillomavirus (HPV) DNA is present in surgical smoke generated by loop electrosurgical excision procedures (LEEPs). Furthermore, we investigated the impact of this HPV DNA on surgeons. Methods: A total of 134 outpatients with persistent HPV infections treated with LEEP for cervical intraepithelial neoplasia between 2015 and 2016, along with the corresponding LEEP operators, were included. The flow fluorescence in situ hybridization technique was used to detect HPV DNA in exfoliated cervical cells from the patients, in surgical smoke and in nasal epithelial cells from the surgeons before and after LEEP. Results: The positive rates of HPV DNA in the three types of samples mentioned above were 94.8%, 29.9% and 1.5%, respectively. The distribution of HPV subtypes in surgical smoke was identical to that in the cervical specimens. The positive rate of HPV DNA in surgical smoke was significantly increased for greater distances of the suction device from the surgical site. The nasal epithelial cells of two surgeons were positive for HPV DNA, and the genotypes were consistent with those in the corresponding surgical smoke. After a 3–6-month follow-up, the nasal swabs from these two doctors tested negative for HPV DNA. Conclusions: This study demonstrated the presence of HPV DNA in surgical smoke produced by LEEP and the risk of airborne transmission of HPV DNA during the operation. Fortunately, the HPV DNA in the nasopharynx of the operators was not persistent.

Cervical cancer is one of the common malignancies in women worldwide. Exploration of pathogenesis and molecular mechanism of cervical cancer is pivotal for development of effective treatment for this disease. Recently, systems biology approaches based on high-throughput technologies have been carried out to investigate the expression of some genes and proteins in genomics, transcriptomics, proteomics, and metabonomics of cervical cancer. Compared with traditional methods，systems biology technology has been shown to provide large of information regarding prognostic biomarkers and therapeutic targets for cervical cancer. These molecular signatures from system biology technology could be useful to understand the molecular mechanisms of cervical cancer development and progression, and help physicians to design targeted therapeutic strategies for patients with cervical cancer. Keywords: Cervical cancer, Systems biology, Genomics, Transcriptomics, Proteomics

Yizuo Song, Yi Liu, Min Lin, Bo Sheng, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China Purpose: To evaluate the efficacy and safety of neoadjuvant platinum-based chemotherapy during pregnancy in women with cervical cancer. Methods: The PubMed, Embase, and Cochrane Library databases were fully searched to find eligible studies regarding platinum use during pregnancy in women with cervical cancer from January 1980 to September 2018. Data were extracted from the selected studies independently by two authors. Descriptive statistics were calculated for categorical data (frequency and percentage) and numeration data (mean and SD for normally distributed data and median and range for abnormally distributed data). Survival analyses were performed using Kaplan–Meier survival curves and log-rank tests to estimate overall survival and progression-free survival for all patients. Results: A total of 39 studies including 88 cervical cancer patients with platinum administration during pregnancy were selected in this meta-analysis, and 64 women provided International Federation of Gynecology and Obstetrics stage information. Among the latter, 56 of 64 (87.5%) were diagnosed with early stages (I and IIA) and the remaining 8 of 64 (12.5%) had advanced stages (IIB, III, and IV). In relation to cisplatin, 86 pregnant women were identified, whereas only 2 pregnant women with carboplatin application were retrieved. Overall, 88 newborns were delivered from 84 pregnancies, including two sets of twins and one set of triplets, among which 71 neonates (71 of 88, 80.7%) were completely healthy at birth. All children were healthy at the end of follow-up (median 17 months, range 0–149.5 months), except one who was diagnosed with retroperitoneal embryonal rhabdomyosarcoma at 5 years old and one who had acute myeloid leukemia at 22 months of age. At the end of follow-up (range 4.75–156 months), 16 of 81 (19.8%) patients were diagnosed with recurrence of cervical cancer, and 11 (90%) of those died because of cancer relapse. Neither median overall survival nor median progression-free survival were reached. Conclusion: Our results demonstrated that neoadjuvant platinum-based chemotherapy could be a favorable choice for the management of patients with cervical cancer during the second and third trimesters. To reduce the side effects of chemotherapy, cisplatin might be good to use as monotherapy in these patients. Keywords: platinum, neoadjuvant chemotherapy, pregnancy, cervical cancer, meta-analysis

Background As LEEP (loop electrosurgical excision procedure) is being increasingly used for the diagnosis and treatment of uterine cervical intraepithelial neoplasia, surgical smoke during LEEP has become an inevitable health issue. Therefore, in this study, exposure to the chemical substances in surgical smoke produced during LEEP was assessed. Methods Smoke samples from patients with high-grade cervical intraepithelial neoplasia undergoing LEEP were collected by smoke-absorbing devices situated 1 m away from the operating table and near the nose of the operator during LEEP. Each plume sample was collected after 5 patients underwent LEEP, requiring 5 min for smoke collection for each patient. The chemicals of exposure to surgical smoke were assessed, and the hazard classes of these chemical components were evaluated by the International Agency for Research on Cancer. Results Qualitative analysis of the smoke produced during LEEP revealed a variety of potentially toxic chemicals under standard detection, such as benzene, toluene, xylene, ethylbenzene, styrene, butyl acetate, acrylonitrile, 1,2-dichloroethane, phenol, chlorine, cyanide, hydrogen cyanide and carbon monoxide. Additionally, the average concentration of carbon dioxide was 0.098 ± 0.015% during surgery and was higher than that before surgery (0.072 ± 0.007%, P < 0.001), and the concentration of formaldehyde was significantly higher during surgery (0.023 ± 0.009 mg/m3, P < 0.05) than before surgery (0.012 ± 0.001 mg/m3, P < 0.05). Conclusions Most of the detected chemical concentrations in smoke generated during LEEP were below the exposure limits when local exhaust ventilation procedures were efficiently used. However, the concentrations of carbon dioxide and formaldehyde found in smoke were significantly higher after surgery. Wearing a high-filtration mask and using evacuation devices routinely and consistently when performing LEEP are recommended to protect perioperative personnel.

Background Our study intended to evaluate the prognostic value of lysyl oxidase (LOX) and its four relevant members, the lysyl oxidase–like genes (LOXL1‐4), in ovarian cancer (OC) patients. Material and Methods The Kaplan‐Meier plotter (KM plotter) database was used to investigate the prognostic power of the LOX family for OC patients. Overall survival (OS) and progression‐free survival (PFS) were the clinical endpoints. The prognostic roles of the LOX family in OC patients were also analyzed according to various clinicopathological characteristics, including histological subtypes, clinical stages, pathological grades, and chemotherapeutic treatments. Results Overexpression of LOX, LOXL1, LOXL2, and LOXL3 mRNA indicated poor OS and PFS in OC patients, particularly in serous and grade II + III OC patients. Overexpression of LOXL4 mRNA resulted in worse PFS in OC patients. Overexpression of LOX and LOXL1 mRNA showed worse OS and PFS in stage III + IV OC patients, and overexpression of LOXL3 mRNA indicated worse OS and PFS in stage I + II OC patients. Overexpression of LOX, LOXL3, and LOXL4 mRNA indicated worse OS and PFS among OC patients who received platinum, taxol, and taxol + platinum chemotherapy. Overexpression of LOXL1 and LOXL2 mRNA was related to lower OS and PFS in OC patients who received platinum chemotherapy. Conclusion LOX, LOXL1, LOXL2, and LOXL3 may become potential predictive markers for negative outcomes in OC patients. Moreover, the LOX family can serve as new molecular predictors for the efficiency of platinum‐based chemotherapy in OC patients., Our study intended to evaluate the prognostic value of lysyl oxidase (LOX) and its four relevant members, the lysyl oxidase‐like genes (LOXL1‐4), in ovarian cancer (OC) patients with various clinicopathological characteristics, which was based on the Kaplan‐Meier plotter database. In conclusion, LOX and LOXL1‐3 are associated with poor prognosis of OC patients. The LOX family predict poor efficiency of platinum‐based chemotherapy in OC patients.

Cancer is one of most the significant threats to human health worldwide, and the primary method of treating solid tumours is surgery. Propofol, one of the most widely used intravenous anaesthetics in surgery, was found to be involved in many cancer‐related pathophysiology processes, mainly including anti‐tumour and minor cancer‐promoting effects in various types of cancer. An increasing number of studies have identified that propofol plays a role in cancer by regulating the expression of multiple signalling pathways, downstream molecules, microRNAs and long non‐coding RNAs. Emerging evidence has indicated that propofol can enhance the anti‐tumour effect of chemotherapeutic drugs or some small molecular compounds. Additionally, in vivo animal models have shown that propofol inhibits tumour growth and metastasis. Furthermore, most clinical trials indicate that propofol is associated with better survival outcomes in cancer patients after surgery. Propofol use is encouraged in cancers that appear to have a better prognosis after its use during surgery. We hope that future large and prospective multicenter studies will provide more precise answers to guide the choice of anaesthetics during cancer surgery., Propofol inhibits tumor cell proliferation, metastasis, and promotes cell apoptosis and increases the sensitivity to chemotherapeutic drugs. In addition, in vivo animal models have shown that propofol inhibits tumor growth and metastasis. Furthermore, propofol is associated with better survival outcomes in cancer patients after surgery.

Background Sevoflurane is commonly used for cervical cancer surgery, but its effect on cervical cancer cell biology remains unclear. This mechanistic study explores how sevoflurane affects the proliferation and metastatic potential of immortalized cervical cancer cell lines. Methods Cultured cervical cancer Caski and HeLa lines were exposed to 1, 2, or 3% sevoflurane for 2 or 4 h. Cell proliferation was determined through the Kit-8 assay and Ki-67 immunofluorescent staining. Cell migration and invasion were evaluated with the Transwell assay. Immunofluorescent staining and Western blot analysis were used to identify sevoflurane-induced morphological and biochemical changes. Results Sevoflurane exposure for either 2 or 4 h significantly increased HeLa cell proliferation in a time- and concentration-dependent manner to be 106 ± 2.7% and 107 ± 1.4% relative to the controls (n = 10; P = 0.036; P = 0.022) at 24 h after exposure and to be 106 ± 2.2% and 106 ± 1.7% relative to the controls (n = 10; P = 0.031; P = 0.023) at the highest concentration of 3% sevoflurane studied, respectively, but not Caski cells. Sevoflurane promoted invasion ability (1.63 ± 0.14 and 1.92 ± 0.12 relative to the controls) and increased cell size (1.69 ± 0.21 and 1.76 ± 0.13 relative to the controls) of Caski and HeLa cells (n = 6; all P < 0.001), respectively. Sevoflurane increased histone deacetylase 6 expression in both cells, and histone deacetylase 6 knockdown abolished the prometastatic effects of sevoflurane. Sevoflurane also induced deacetylation of α-tubulin in a histone deacetylase 6–dependent manner. The protein kinase B (AKT) or extracellular regulated protein kinase (ERK1/2) phosphorylation inhibition attenuated sevoflurane-induced histone deacetylase 6 expression. Conclusions Sevoflurane enhanced proliferation, migration, and invasion of immortalized cervical cancer cells, which was likely associated with increasing histone deacetylase 6 expression caused by phosphatidylinositide 3-kinase/AKT- and ERK1/2-signaling pathway activation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Objective To investigate the associations between serum vitamin D, calcium and uterine fibroids in a Chinese female population. Methods In this case-control study, adult female patients with fibroids (cases) were compared with females without fibroids (controls) in terms of serum 25-hydroxyvitamin D (25OHD) and calcium levels. Results Out of 546 total participants (mean age, 41.68 ± 5.99 years; 279 with fibroids and 267 without fibroids), only 232 had serum 25OHD levels above the sufficient threshold (>20 ng/ml). In addition, females with fibroids had lower serum 25OHD levels versus those without fibroids. The prevalence of fibroids in females with deficient (20 ng/ml) 25OHD levels. Serum calcium levels were within normal range in both groups. Conclusion Hypovitaminosis D was highly prevalent among a population of Chinese females of reproductive-age, and serum 25OHD levels were lower in female patients with fibroids.

Multiple studies have confirmed that speckle-type pox virus and zinc finger (POZ) protein (SPOP) functions as a substrate adaptor of cullin 3-based E3 ligase and has a crucial role in various cellular processes via specific targeting of proteins for ubiquitination and subsequent proteasomal degradation. Dysregulation of SPOP-mediated proteolysis might be involved in the development and progression of human prostate and kidney cancers. In prostate cancer, SPOP seems to function as a tumour suppressor by targeting several proteins, including androgen receptor (AR), steroid receptor coactivator 3 (SRC3) and BRD4, for degradation, whereas it might function as an oncoprotein in kidney cancer, for example, by targeting phosphatase and tensin homologue (PTEN) for proteasomal degradation. In addition, nuclear SPOP targets AR for degradation and has a role as a tumour suppressor in prostate cancer; however, in kidney cancer, SPOP largely accumulates in the cytoplasm and fails to promote degradation of AR located in the nucleus, resulting in activation of AR-driven pathways and cancer progression. Owing to the context-dependent function of SPOP in human malignancies, further assessment of the molecular mechanisms involving SPOP in prostate and kidney cancers is needed to improve our understanding of its role in the development of these cancer types. Treatments that target SPOP might become therapeutic strategies in these malignancies in the future.

To explore the effects of aquaporin (AQP) 1 on pregnancy outcome and the association between expression of AQP1 and other AQPs in the placenta and foetal membranes, the rate of copulatory plugs and pregnancy, amniotic fluid (AF) volume, osmolality and composition were determined in AQP1-knockout (AQP1−/−) mice at different gestational days (GD). The expression and location of AQP1 and other AQPs in the placenta and foetal membranes of AQP1−/− mice, AQP1-siRNA transfected WISH cells and oligohydramnios patients were also detected. Compared to control mice, AQP1−/− mice exhibited reduced copulation plug and successful pregnancy rates, but these effects were accompanied by a larger AF volume and lower AF osmolality at late gestation. AQP9 expression was significantly decreased in the placenta and foetal membranes of AQP1−/− mice, while AQP8 level was elevated in the foetal membranes of AQP1−/− mice. Moreover, AQP9 expression was suppressed in WISH cells after AQP1 downregulation. Furthermore, AQP9 expression was associated with AQP1 level in the placenta and foetal membranes in oligohydramnios. AQP1 may play a critical role in regulating pregnancy outcome and maternal-foetal fluid homeostasis. Changes in AQP1 expression may lead to compensatory alterations in AQP8 and AQP9 expression in the placenta.

Preferentially expressed antigen in melanoma (PRAME), which belongs to the cancer/testis antigen (CTA) gene family, plays a pivotal role in multiple cellular processes and immunotherapy response in human cancers. PRAME is highly expressed in different types of cancers and is involved in cell proliferation, apoptosis, differentiation and metastasis as well as the outcomes of patients with cancer. In this review article, we discuss the potential roles and physiological functions of PRAME in various types of cancers. Moreover, this review highlights immunotherapeutic strategies that target PRAME in human malignancies. Therefore, the modulation of PRAME might be useful for the treatment of patients with cancer.

Galectins are the member of soluble proteins that bind with β-galactoside containing glycans. These proteins have been considered to be associated in various important events such as different types of cancers. It has been found that galectins could contribute to neoplastic transformation or regulate cell growth, cell apoptosis, and immune cells, causing tumor invasion, progression, metastasis and angiogenesis. Somehow, galectins are also found to exert a protective effect on cancer in a tissue-dependent way. These glycans binding proteins have been shown to be involved in the regulation of different tumor suppressor genes and oncogenes with their possible roles in human cancers. Objective of the current review is to summarize the role of galectin-1, -3 -7, and -9 in tumorigenesis of gynecological cancers. Galectin protein may be a potential therapeutic target in gynecological malignancies due to reported radio- and chemo- sensitivities, immunotherapeutic, anti-angiogenic and anti-proliferative activities. This review considers the evidence for the future research that how galectins may be important in the progression and treatment of gynecological cancers along with its potent use as a novel prognostic marker.

Background Preeclampsia is a disease that frequently complicates pregnancy and poses a serious threat to maternal and fetal health. The causes and pathogenic mechanisms of preeclampsia are poorly defined. Genetic predisposition could be an important etiological factor. Previous studies have demonstrated that syncytin-1 and syncytin-2, encoded by the genes ERVWE1 and ERVFRDE-1, are involved in the pathogenesis of preeclampsia. Methods In this study, we applied multiplex PCR and MALDI-TOF MS techniques to analyze six selected tag SNPs of ERVWE1 and ERVFRDE-1 in 120 preeclampsia patients and 181 normal controls. Results One SNP polymorphism (rs9393931) with the recessive TT genotype located in the 3-UTR of ERVFRDE-1 gene was found to be significantly associated with an increased risk of preeclampsia (OR (95% CI) = 2.05 (1.27–3.32); p = 2.8 × 10−3). No significant correlation of this polymorphism with the clinical severity of preeclampsia, e.g. the extent of hypertension, was detected between carrier and non-carrier patients. Conclusions These results suggested that genetic predisposition in ERVFRDE-1 may be associated with an increased risk of preeclampsia. This polymorphism is possibly involved in the regulation of syncytin-2 expression in preeclamptic placenta.

Excision repair cross-complementing (ERCC) genes, key components of the nucleotide excision repair pathway, are regarded as crucial factors for DNA repair capacity. Previous studies have investigated prognostic values of ERCC genes in a number of malignancies. However, the relationship between ERCC genes and prognosis of ovarian cancer patients remains controversial. Therefore, in the current study, we systematically analyze the prognostic values of ERCC genes in ovarian cancer by the Kaplan-Meier plotter, which includes updated gene expression data and survival information of 1656 ovarian cancer patients. Our results showed that high expression of ERCC1 and ERCC8 mRNA was related to a worse overall survival among ovarian cancer patients, especially in late stage and poor differentiation serous ovarian patients. Increased ERCC4 mRNA expression indicated a better overall survival among serous ovarian cancer patients. The other ERCC genes were uncorrelated with prognosis in ovarian cancer. These results indicate that some ERCC genes have critical prognostic values in ovarian cancer.

Histone deacetylases modulate the dynamic balance of histone acetylation and deacetylation in cells, which participate in epigenetic regulations. Accumulated evidence has demonstrated that histone deacetylases are associated with angiogenesis, cell proliferation and survival in a variety of human cancers. However, the expression and distinct prognostic value of histone deacetylases in ovarian cancer have not been well elucidated. In the present study, we collected the overall survival (OS), progress free survival (PFS), and histone deacetylases (HDAC1-11) mRNA expression in ovarian cancer from the Kaplan-Meier plotter online database. We investigated the relationship between histone deacetylases mRNA level and the clinicopathological parameters of the ovarian cancer patients, such as histology subtypes, clinical stages, grades and TP53 mutation. Our analysis data showed that over-expression of HDAC1, HDAC2, HDAC4, HDAC5 and HDAC11 were correlated to poor overall survival and unfavorable progress free survival in all ovarian cancer patients. Notably, the higher level of HDAC11 was associated with the worse OS and PFS for serous/ stage III+IV/ grade III/ TP53 mutation ovarian cancer patients. In conclusion, HDACs may play a crucial role in the prognosis of ovarian cancer, but it is worth noting that HDAC11 may be a biomarker for poor prognosis in ovarian cancer patients.

Purpose DNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR has been reported as a prognostic marker in certain cancers; however, the results are controversial. Therefore, identification of the prognostic value of MMR genes in ovarian cancer based on a large sample size is pivotal. Methods In the current study, we systemically investigated the prognostic roles of seven MMR genes, MSH2, MSH3, MSH6, MLH1, MLH3, PMS1 and PMS2, in ovarian cancer patients treated with platinum-based chemotherapy through “The Kaplan–Meier plotter” (KM plotter) database, which contains gene expression data and survival information of ovarian cancer patients. Results Among seven MMR genes, high mRNA levels of MSH6, MLH1 and PMS2 were significantly associated with a better overall survival for all ovarian cancer patients treated with platinum-based chemotherapy, especially in late-stage and poor-differentiated ovarian cancer patients. Increased MSH6 and PMS2 mRNA expression was correlated with a favorable overall survival in serous ovarian cancer patients. Conclusions Our results indicate that sufficient MMR system is associated with an improved survival in ovarian cancer treated with platinum-based chemotherapy. MMR gene may be a potential prognosis predictor in ovarian cancer.

// Zhaojun Shen 1 , Hui Luo 1 , Saisai Li 1 , Bo Sheng 1 , Menghuang Zhao 1 , Haiyan Zhu 1 and Xueqiong Zhu 1 1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China Correspondence to: Xueqiong Zhu, email: zjwzzxq@163.com Haiyan Zhu, email: zhuhaiyandoc@sina.com Keywords: epithelial ovarian cancer, estrogen receptor, prognosis, meta-analysis Received: March 24, 2017 Accepted: April 26, 2017 Published: May 29, 2017 ABSTRACT Objective: Accumulated studies have investigated the prognostic significance of estrogen receptor expression in epithelial ovarian cancer, but results remain controversial. The aim of this study was to perform a meta-analysis to clarify the prognostic value of estrogen receptor expression in epithelial ovarian cancer. Methods: A systematic search was performed in PUBMED, EMBASE, and COCHRANE databases to identify relevant studies up to December 2016. The pooled hazard rates (HR) with 95% confidence intervals (CIs) for overall survival and time to tumor progression were calculated and then weighted and pooled in this meta-analysis with a random-effect model. Results: Thirty-five studies with a total of 5824 patients were included. In brief, the expression of estrogen receptor was associated with an improved overall survival (HR = 0.86, 95% CI = 0.76-0.97), whereas there was no significant difference between estrogen receptor and time to tumor progression among epithelial ovarian cancer patients. Subgroup analysis revealed that estrogen receptor expression was significantly correlated with overall survival in different subgroups, such as in unclassified epithelial ovarian cancer (HR= 0.80, 95% CI = 0.66-0.95), studies using immunohistochemistry detection method (HR= 0.85, 95% CI = 0.73-1.00), European population (HR= 0.75, 95% CI = 0.60-0.94) and estrogen receptor α subtype (HR= 0.78, 95% CI = 0.62-0.98). Conclusions: Estrogen receptor, especially estrogen receptor α, was associated with an improved overall survival in epithelial ovarian cancer. Estrogen receptor expression may be a promising prognostic factor in epithelial ovarian cancer patients.

Background: Medical abortion that occurs in early pregnancy is generally safe and successful, but incomplete medical abortion can result in complications. This study aimed to examine factors related to completeness of medical abortion with mifepristone and misoprostol, and then to provide a new direction for research into establishing complete abortion with mifepristone and misoprostol. Methods: Sixty-three patients with early pregnancy requesting medical abortion with mifepristone and misoprostol were selected. Immunohistochemistry was used to detect the expression and location of progesterone receptor, estrogen receptor, insulin-like growth factor-1, and vascular endothelial growth factor in chorionic villi among these women. Reverse transcriptase polymerase chain reaction was then used to determine the expression of insulin-like growth factor-1 and vascular endothelial growth factor mRNA. Results: According to the outcome of medical abortion, the women were divided into either the incomplete medical abortion group (n=34) or the complete medical abortion group (n=29). Immunohistochemical analysis showed that progesterone receptor and estrogen receptor protein expression was not detected in chorionic villi in the two groups. However, compared with the complete abortion group, there was a marked decrease in the expression of insulin-like growth factor-1 and a significant increase in the expression of vascular endothelial growth factor (p

Serum epididymis protein 4 (HE4) level is a useful biomarker for the management of ovarian and endometrial cancer patients. Urine HE4-test, with its easier access than serum test, has emerged as a new method with promising application for the diagnosis of ovarian cancer. Areas covered: This review summarizes data regarding the detection and alteration of HE4 in urine samples collected from ovarian cancer patients and controls. The performance and limitation of the assay and potential direction of future study are also discussed. Expert commentary: Several studies have demonstrated an appreciable efficiency of urine HE4-test in the discrimination of ovarian cancer patients from general population. However, the data is based on small cohorts, and the performance of urine HE4-test need to be validated in larger groups. An algorithm incorporating other important factors may allow a quantitative assessment of cancer possibility. Future studies on the HE4 renal secretion and HE4 degradation dynamics in urine are also required for the establishment of standard protocols for the application of urine HE4-test in clinical settings.

Transketolase genes are key rate-limiting enzymes in the non-oxidative part of the pentose phosphate pathway, which is an important metabolic pathway in ribose-5-phosphate production. Three human transketolase genes have been identified: Transketolase (TKT), transketolase-like gene 1 (TKTL1) and transketolase-like gene 2 (TKTL2). Transketolase genes serve crucial roles in the tumorigenesis, metastasis and outcome of multiple types of cancer. However, the expression levels and prognostic values of transketolase family genes in patients with ovarian cancer remain unclear. The purpose of the study was to analyze the expression level and prognostic significance of transketolase family genes in ovarian cancer. In the present study, the mRNA expression levels of three transketolase genes in ovarian cancer and normal ovarian tissue were compared by Oncomine. The prognostic values of these genes were systemically assessed using the Kaplan-Meier plotter database. In addition, the associations between the mRNA levels of these transketolase genes and the clinicopathological characteristics of patients with ovarian cancer, such as histological subtype, clinical stage, grade, tumor protein p53 (TP53) mutation status and chemotherapy history were studied. The prognostic roles of transketolase genes were also evaluated in a validation dataset. The results demonstrated that TKT and TKTL1 expression in ovarian cancer tissues was elevated compared with that in normal ovarian tissues. In addition, high mRNA expression of the three transketolase genes was identified to be associated with poorer progression-free survival (PFS) in patients with serous ovarian cancer, especially in patients at an advanced stage. TKTL2 was significantly associated with poor overall survival in all patients with ovarian cancer. Additionally, transketolase family genes served a role in predicting PFS in patients with ovarian cancer treated with platinum and/or taxol. High expression of the three transketolase genes was associated with unfavorable PFS in patients with TP53-mutated ovarian cancer, but not in patients with TP53 wild-type ovarian cancer. These results suggested that transketolase family genes may serve important roles in the prognosis of patients with ovarian cancer.

Current research indicate that long noncoding RNAs (lncRNAs) are associated with the progression of various cancers and can be used as prognostic biomarkers. This study aims to construct a prognostic lncRNA signature for the risk assessment of Uterine corpus endometrial carcinoma (UCEC). The RNA-Seq expression profile and corresponding clinical data of UCEC patients obtained from The Cancer Genome Atlas database. First, some prognosis-related lncRNAs were obtained by univariate Cox analysis. The minimum absolute contraction and selection operator (LASSO) regression and the Cox proportional hazard regression method were used to further identify the lncRNA prognostic model. Finally, seven lncRNAs (AC110491.1, AL451137.1, AC005381.1, AC103563.2, AC007422.2, AC108025.2, and MIR7-3HG) were identified as potential prognostic factors. According to the model constructed by the above analysis, the risk score of each UCEC patient was calculated, and the patients were classified into high and low-risk groups. The low-risk group had significant survival benefits. Moreover, we constructed a nomogram that incorporated independent prognostic factors (age, tumor stage, tumor grade, and risk score). The c-index value for evaluating the predictive nomogram model was 0.801. The area under the curve was 0.797 (3-year survival). The calibration curve also showed that there was a satisfactory agreement between the predicted and observed values in the probability of 1-, 3-, and 5-year overall survival. On the basis of the coexpression relationship, we established a coexpression network of lncRNA-messenger RNA (mRNA) of the 7-lncRNA. The Kyoto Encyclopedia of Genes and Genomes analysis of the coexpressing mRNAs showed that the main pathways related to the 7-lncRNA signature were neuroactive ligand-receptor interaction, serotonergic synapse, and gastric cancer pathway. Therefore, our study revealed that the 7-lncRNA could be used to predict the prognosis of UCEC and for postoperative treatment and follow-up.

// Haiyan Zhu 1, * , Hui Luo 1, * , Xuejie Zhu 2 , Xiaoli Hu 1 , Lihong Zheng 1 , Xueqiong Zhu 1 1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China 2 Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China * These authors have contributed equally to this work Correspondence to: Xueqiong Zhu, email: zjwzzxq@163.com Keywords: PKM2, cancer, prognosis, meta-analysis Received: June 13, 2016 Accepted: October 26, 2016 Published: November 29, 2016 ABSTRACT Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer. Pooled analysis showed that high levels of PKM2 was significantly associated with a poorer overall survival (HR = 1.73; 95%CI = 1.48-2.03) and DFS/ PFS/ RFS (HR = 1.90; 95%CI = 1.39-2.59) irrespective of cancer types. Different analysis models (univariate or multivariate models), sample-sizes (≤100 or >100), and methods for data collection (direct extraction or indirect extraction) had no impact on the negative prognostic effect of PKM2 over-expression. Nevertheless, stratified by cancer type, high-expression of PKM2 was associated with an unfavorable OS in breast cancer, esophageal squamous carcinoma, hepatocellular carcinoma and gallbladder cancer; whereas was not correlated with a worse OS in pancreatic cancer and gastric cancer. In conclusion, over-expression of PKM2 is associated with poor prognosis in most solid cancers and it might be a potentially useful biomarker for predicting cancer prognosis in future clinical applications.

Aquaporins (AQPs) are highly expressed in tumor cells of different origins, particularly the aggressive tumors. The aim of this study was to investigate the expression of AQP isoforms during progression of squamous cervical cancer (SCC) and explore their associations with clinicopathologic variables of SCC.Expression of AQP isoforms (1, 3, 4, 5, and 8) was detected by immunohistochemistry in 47 SCCs, 37 cervical intraepithelial neoplasia (CIN), and 16 normal cervical tissues. Specific expression of AQP protein in SCC was detected by Western blot. Double immunohistochemistry was used to examine whether AQPs and vascular endothelial growth factor (VEGF) are coexpressed in SCC.Aquaporin 1 showed higher positivity rate in CIN than in SCC and normal cervical tissues (P.05). The expression intensity of AQP3, 4, 5, and 8 was higher in SCC than that in normal cervical tissues, respectively (P.05). The expression of AQP3 and 8 was higher in SCC than that in CIN, respectively (P.05). The AQP4 expression was higher in CIN than in normal cervical tissues (P.05). The expression of AQP3 in CIN III was higher than that in CIN I and II (P.05). There was a significant increase in the expression of AQP1 in stage I than that in stage II (P.05). Aquaporin 3 showed lower positivity in moderately and well-differentiated tumors compared to that in poorly differentiated tumors (P.05). Finally, double immunohistochemistry illustrated that AQP1/AQP3/AQP8 and VEGF were coexpressed in SCC.Different AQP isoforms display specific expression patterns in normal cervical, CIN, and SCC tissues. This and the significant association with the clinicopathologic variables of SCC suggest that AQP isoforms might play different roles in the development of cervical cancer.

IntroductionUterine fibroids are the most common pelvic benign tumour with no satisfactory long-term medical treatment. Recent studies have demonstrated that vitamin D significantly inhibited the growth of fibroids in vitro, vivo and a small-sample clinical trial. Therefore, the aim of this randomised clinical trial (RCT) is to evaluate whether supplementation with vitamin D could reduce the risk and inhibit the growth of uterine fibroids in reproductive stage women.Methods and analysisThe open-label, RCT comprises two parts, including parts I and II. In part I, 2230 vitamin D deficiency or vitamin D insufficiency patients without uterine fibroids will be randomly assigned to two groups: intervention group (according to the level of serum 25-hydroxyvitamin D3, receive 1600 or 800 IU/day of vitamin D3 for 2 years) and control group (followed up at the same time points). By using gynaecological ultrasound examinations, the incidence of uterine fibroids will be employed to measure the outcome in different groups. In part II, 360 uterine fibroids patients with vitamin D deficiency or vitamin D insufficiency will be randomly assigned to intervention group or control group. According to the level of serum 25-hydroxyvitamin D3, 180 patients will receive 1600 or 800 IU/day of vitamin D3 for 2 years. Control group will receive regular follow-up. The outcome measure will be conducted using gynaecological ultrasound examinations to detect the growth of uterine fibroids in each group.Ethics and disseminationThis study has been approved by the institutional review board of the Second Affiliated Hospital of Wenzhou Medical University (No. LCKY2018-35).Trial registration numbersNCT03586947 and NCT03584529.

Objective This study was performed to quantify hidden blood loss (HBL) and explore its influential factors in myomectomy. Methods Two hundred nine patients who underwent myomectomy by laparotomy or laparoscopy from 1 January 2017 to 31 December 2018 were analyzed. Each patient’s estimated blood volume and total blood loss (TBL) were calculated by the Nadler formula and Gross formula, respectively. The HBL was calculated by subtracting the visible blood loss (VBL) from the TBL. A multivariate linear stepwise analysis was applied to identify the influential factors of HBL in myomectomy. Results The mean perioperative VBL and estimated TBL during myomectomy were 137.81 ±104.43 and 492.24 ± 225.00 mL, respectively. The mean HBL was 354.39 ± 177.69 mL, which accounted for 71.52% ± 15.75% of the TBL and was two to three times higher than the VBL. The duration of surgery, number of removed leiomyomas, and location of removed leiomyomas were independent risk factors for HBL in myomectomy. Conclusions HBL accounted for a significant percentage of TBL in myomectomy. A full understanding of the HBL in perioperative blood management may improve patients’ postoperative rehabilitation.

Purpose: Peroxiredoxins (PRDXs) are a family of antioxidant enzymes with six identified mammalian isoforms (PRDX1–6). PRDX expression is up-regulated in various types of solid tumors; however, individual PRDX expression, and its impact on prognostic value in ovarian cancer patients, remains unclear. Methods: PRDXs family protein expression profiles in normal ovarian tissues and ovarian cancer tissues were examined using the Human Protein Atlas database. Then, the prognostic roles of PRDX family members in several sets of clinical data (histology, pathological grades, clinical stages, and applied chemotherapy) in ovarian cancer patients were investigated using the Kaplan–Meier plotter. Results: PRDXs family protein expression in ovarian cancer tissues was elevated compared with normal ovarian tissues. Meanwhile, elevated expression of PRDX3, PRDX5, and PRDX6 mRNAs showed poorer overall survival (OS); PRDX5 and PRDX6 also predicted poor progression-free survival (PFS) for ovarian cancer patients. Furthermore, PRDX3 played significant prognostic roles, particularly in poor differentiation and late-stage serous ovarian cancer patients. Additionally, PRDX5 predicted a lower PFS in all ovarian cancer patients treated with Platin, Taxol, and Taxol+Platin chemotherapy. PRDX3 and PRDX6 also showed poor PFS in patients treated with Platin chemotherapy. Furthermore, PRDX3 and PRDX5 indicated lower OS in patients treated with these three chemotherapeutic agents. PRDX6 predicted a poorer OS in patients treated with Taxol and Taxol+Platin chemotherapy. Conclusion: These results suggest that there are distinct prognostic values of PRDX family members in patients with ovarian cancer, and that the expression of PRDX3, PRDX5, and PRDX6 mRNAs are a useful prognostic indicator in the effect of chemotherapy in ovarian cancer patients.

Aquaporins (AQPs), a family of transmembrane channel, are composed of 13 identified members (AQP0–12). Accumulating evidences reported that AQPs were correlated with various biological roles and represented a prognostic predictor in various cancer types. However, the prognostic value of AQPs expression in ovarian cancer remains unclear. Using ‘Kaplan–Meier plotter’ (KM plotter) online database, we explored the predictive prognostic value of individual AQPs members’ mRNA expression to overall survival (OS) in different clinical data, such as histology, pathological grades, clinical stages, TP53 status, and applied chemotherapy in ovarian cancer patients. Our results revealed that higher AQP0, AQP1, and AQP4 mRNA expression were correlated with poor OS, whereas higher AQP3, AQP5, AQP6, AQP8, AQP10, and AQP11 showed better OS in ovarian cancer patients. Moreover, AQP4 and AQP8 showed poor OS in TP53-mutated ovarian cancer patients and AQP1 presented unfavorable OS in both TP53 mutated and wild ovarian cancer patients. Additionally, AQP3, AQP6, and AQP11 mRNA expression were correlated with better OS, whereas AQP0 and AQP1 showed poor OS in all ovarian cancer patients treated with Platin, Taxol, and Taxol + Platin chemotherapy. AQP5, AQP8, and AQP10 were associated with improved OS, however, AQP4 predicted unfavorable OS in all patients treated with Platin chemotherapy. Our results suggest that individual AQPs, except AQP2 and AQP9, are associated with unique prognostic significance and may thus act as new predictive prognostic indicators and potential drug therapeutic target in ovarian cancer.