Publications by authors named "Xiaomao Li"

70 Publications

Anti-N-Methyl-D-Aspartate Receptor Encephalitis Associated with Ovarian Teratoma in South China-Clinical Features, Treatment, Immunopathology, and Surgical Outcomes of 21 Cases.

Dis Markers 2021 21;2021:9990382. Epub 2021 May 21.

Department of Gynecology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

Objective: To study the clinical characteristics and surgical outcomes of anti-NMDAR encephalitis and the immunopathology of associated teratomas.

Methods: Twenty-one patients were enrolled in this retrospective study, who were diagnosed with anti-NMDAR encephalitis with ovarian teratoma and admitted to two tertiary hospitals in South China from July 2014 to December 2019. The clinical data of patients were reviewed. Comparisons were made between the patients with different outcomes after surgery. Immunohistochemical analyses of associated ovarian teratomas were performed.

Results: The mean age of the patients was 24.33 ± 5.12 years. The peak seasons of disease onset were autumn and winter (30.61% and 32.65%). The symptoms could be divided into 8 categories, including psychiatric abnormalities, seizures, movement dysfunction, consciousness disorders, autonomic dysregulation, speech disturbance, central hypoventilation, and memory deficits. All patients developed four or more categories of symptoms within the first four weeks. Twelve patients (57.1%) had a maximum mRS of 5, and 11 patients (52.4%) were admitted to ICU. Twenty patients received surgery, and only 3 patients were diagnosed pathologically with immature ovarian teratomas, while the other 17 patients had mature ovarian teratomas. After surgery, 17 patients (85.0%) got clinical improvement. The central hypoventilation symptom and mature ovarian teratomas were associated with surgical outcome. Immunohistochemical analysis revealed that there were NMDAR-positive neural tissues in all 8 teratomas and in which 3 cases also contained large numbers of NMDAR-positive sebaceous glands and squamous epithelial tissues.

Conclusion: The disease is of high prevalence in autumn and winter. The central hypoventilation symptom and mature ovarian teratomas were associated with surgical outcome. NMDAR-positive neural tissue is not the only etiological factor of encephalitis. We speculate that encephalitis development in some patients may result from NMDAR expression in sebaceous glands and squamous epithelial tissues.
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http://dx.doi.org/10.1155/2021/9990382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163540PMC
May 2021

Identification of the 11-lncRNA signatures associated with the prognosis of endometrial carcinoma.

Sci Prog 2021 Jan-Mar;104(1):368504211006593

Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.

Endometrial carcinoma (EC) is the fourth most common cancer in women. Some long non-coding RNAs (lncRNAs) are regarded as potential prognostic biomarkers or targets for treatment of many types of cancers. We aim to screen prognostic-related lncRNAs and build a possible lncRNA signature which can effectively predict the survival of patients with EC. We obtained lncRNA expression profiling from the TCGA database. The patients were classified into training set and verification set. By performing Univariate Cox regression model, Robust likelihood-based survival analysis, and Cox proportional hazards model, we developed a risk score with the Cox co-efficient of individual lncRNAs in the training set. The optimum cut-off point was selected by ROC analysis. Patients were effectively divided into high-risk group and low-risk group according to the risk score. The OS of the low-risk patients was significantly prolonged compared with that of the high-risk group. At last, we validated this 11-lncRNA signature in the verification set and the complete set. We identified an 11-lncRNA expression signature with high stability and feasibility, which can predict the survival of patients with EC. These findings provide new potential biomarkers to improve the accuracy of prognosis prediction of EC.
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http://dx.doi.org/10.1177/00368504211006593DOI Listing
March 2021

The role of an immune signature for prognosis and immunotherapy response in endometrial cancer.

Am J Transl Res 2021 15;13(2):532-548. Epub 2021 Feb 15.

Department of Orthopaedics Surgery, The Affiliated Hospital of Qingdao University Qingdao 266071, Shandong, China.

Immunotherapy is a practical and promising treatment for advanced and recurrent endometrial cancer (EC). In this study, we identified an immune-related gene (IRG) signature to predict the overall survival (OS) and response to immune checkpoints inhibitors (ICIs) in patients with EC. The RNA expression profiles of EC were obtained from The Cancer Genome Atlas database and then were filtered for IRGs based on the Immport database. Using the conjoint Cox regression model, an immune signature consisting of seven risk IRGs (CBLC, PLA2G2A, TNF, NR3C1, APOD, TNFRSF18, and LTB) was developed. The immune signature was independent of other clinical factors and was superior to the traditional staging method for OS prediction in EC. Immunohistochemistry staining from the Human Protein Atlas database and quantitative real-time PCR analysis of EC samples were also performed to validate the expression levels of risk IRGs. By further analyzing the tumor microenvironment in EC, patients in the low-risk subgroup showed a higher immune cell infiltration status, which was associated with a better prognosis. Moreover, the tumor mutational burden and immunophenoscore analysis demonstrated that the low-risk subgroup was more sensitive to ICI-based immunotherapy. These findings might shed light on the development of targeted treatment and novel biomarkers for patients with EC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868845PMC
February 2021

Construction of novel antimicrobial peptide-modified extracellular matrix biologic scaffold material.

Biochem Biophys Res Commun 2021 03 12;546:162-168. Epub 2021 Feb 12.

Department of Gynecology and Obstetrics, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China. Electronic address:

In the field of implantable medical devices, the antibacterial extracellular matrix (ECM) biologic scaffold, which is constructed by modifying biomaterials with antibacterial peptides, has excellent potential. An antibacterial peptide-modified ECM scaffold was formed with chitosan (CS), antimicrobial peptide (AMP), and ECM scaffold. Chitosan has a firm positive-charge surface and can combine with the ECM scaffold material to form a positive-charge layer on the surface. The surface potential was characterized using a surface potential map. Infrared spectroscopy and scanning electron microscopy (SEM) were used to observe the scaffold surface characteristics and cell morphology. Fluorescence staining and MTS assay kit were used to assess cytotoxicity and biocompatibility. To evaluate the antibacterial and repairing effects on the infected wounds in vivo, a subcutaneous antibacterial test of rabbit back was conducted. The antibacterial peptide-modified ECM scaffold was successfully formed and presented an excellent three-dimensional micro-surface porous structure. The antibacterial peptide-modified ECM scaffold could be effectively-prepared by surface modification and activation. Fluorescence staining tests showed good cell adhesion, proliferation ability, and cell affinity. The in vivo experiment indicated that the antibacterial ECM scaffold had antibacterial and healing-promotion abilities.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.002DOI Listing
March 2021

A novel antibacterial biomaterial mesh coated by chitosan and tigecycline for pelvic floor repair and its biological performance.

Regen Biomater 2020 Oct 2;7(5):483-490. Epub 2020 Sep 2.

Department of Gynecology and Obstetrics, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

The biomaterials composed of mammalian extracellular matrix (ECM) have a great potential in pelvic floor tissue repair and functional reconstruction. However, bacterial infection does cause great damage to the repair function of biomaterials which is the major problem in clinical utilization. Therefore, the development of biological materials with antimicrobial effect is of great clinical significance for pelvic floor repair. Chitosan/tigecycline (CS/TGC) antibacterial biofilm was prepared by coating CS/TGC nanoparticles on mammalian-derived ECM. Infrared spectroscopy, scanning electron microscopy, bacteriostasis circle assay and static dialysis methods were used to characterize the membrane. MTS assay kit and DAPI fluorescence staining were used to evaluate cytotoxicity and cell adhesion. The biocompatibility was assessed by subabdominal implantation model in goats. Subcutaneous antimicrobial test in rabbit back was used to evaluate the antimicrobial and repairing effects on the infected wounds . Infrared spectroscopy showed that the composite coating had been successfully modified. The antibacterial membrane retained the main structure of ECM multilayer fibers. release of biomaterials showed sustained release and stability. studies showed that the antibacterial biological membrane had low cytotoxicity, fast degradation, good compatibility, anti-infection and excellent repair ability.
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http://dx.doi.org/10.1093/rb/rbaa034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597805PMC
October 2020

Neoadjuvant Chemotherapy Followed by Radical Surgery versus Radiotherapy (with or without Chemotherapy) in Patients with Stage IB2, IIA, or IIB Cervical Cancer: A Systematic Review and Meta-Analysis.

Dis Markers 2020 27;2020:7415056. Epub 2020 Jul 27.

Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

Background: This study was to compare the efficacy and safety between neoadjuvant chemotherapy followed by radical surgery (NACT+RS) and radiotherapy only (RT) or concurrent chemoradiotherapy (CCRT) for treatment of patients with stage IB2, IIA, or IIB cervical cancer.

Method: The electronic databases of PubMed, Embase, and the Cochrane Library were searched to screen relevant studies from their inception to October 2018. Clinical data including overall survival (OS), disease-free survival (DFS), and adverse events were extracted. Egger's test was used to evaluate the publication bias, and sensitivity analysis was conducted to estimate the robustness of results.

Results: Finally, three randomized controlled trials (RCTs) and two case-control studies consisting of 1,275 patients with stage IB2, IIA, or IIB cervical cancer were included in the current study. Overall, pooled results showed no significant differences in OS ((hazard ratio (HR) = 0.603, 95%CI = 0.350 - 1.038) and DFS (HR = 0.678, 95%CI = 0.242 - 1.904) for patients treated with NACT+RS compared with RT only or CCRT, but the subgroup analysis showed that the OS and DFS were significantly longer in the NACT+RS groups than the RT or CCRT group (OS: HR = 0.431, 95%CI = 0.238 - 0.781, = 0.006; DFS: HR = 0.300, 95%CI = 0.187 - 0.482, < 0.001) for the population with median follow-up time of more than 60 months. For adverse events, the incidence of thrombocytopenia in the NACT+RS group was significantly higher than that in the RT only or CCRT group (relative risk (RR) = 3.240, 95% CI 1.575-6.662), while the incidence of diarrhea was significantly lower than that in the RT only or CCRT group (RR = 0.452, 95% CI =0.230-0.890).

Conclusion: These findings suggest that the short-term therapeutic effects of the two treatments may be possibly equal for patients with stage IB2-IIB cervical cancer, but the long-term effects for improving OS and DFS may be better using NACT+RS compared with the RT only or CCRT.
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http://dx.doi.org/10.1155/2020/7415056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403931PMC
June 2021

Comprehensive Analysis of Prognostic Alternative Splicing Signatures in Endometrial Cancer.

Front Genet 2020 29;11:456. Epub 2020 May 29.

Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Background: Alternative splicing (AS) is one of the critical post-transcriptional regulatory mechanisms of various cancers and also plays a crucial role in the development of cancers, including endometrial cancer (EC).

Methods: The splicing data and gene expression profiles of EC were obtained from The Cancer Genome Atlas. The corresponding clinical data were extracted from TCGA-CDR. With univariate Cox regression analysis, least absolute shrinkage and selection operator model, and multivariate Cox regression analysis, the survival-related AS events were selected. Functional enrichment analysis was also performed to investigate the functions of these AS events. Splicing factors and AS regulation network were constructed to understand the correlation among these AS events.

Result: A total of 1826 AS events were identified as survival-related events. Functional enrichment analysis showed that these AS events were associated with several immune system-related processes. Then, the prognostic signatures were developed based on these survival-related events and acted as an independent prognostic factor for EC. Splicing factors and AS regulation network were also constructed to understand the regulatory mechanisms of AS events in EC.

Conclusion: This study systematically analyzed the role of AS events in EC and developed the prognostic model for EC.
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http://dx.doi.org/10.3389/fgene.2020.00456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272712PMC
May 2020

A Meta-Analysis of Robotic Surgery in Endometrial Cancer: Comparison with Laparoscopy and Laparotomy.

Dis Markers 2020 21;2020:2503753. Epub 2020 Jan 21.

The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

Background: The safety and effectiveness of robotic surgery are evaluated by comparing perioperative outcomes with laparoscopy and laparotomy in endometrial cancer.

Method: PubMed, MEDLINE, Embase, Cochrane, and other databases were searched for eligible studies up to April 2019. Studies that compared robotic surgery with laparoscopy or laparotomy in surgical staging of endometrial cancer were included. The pooled odds ratio and weighted mean difference were calculated using a random-effects or a fixed-effects model to summarize the results.

Results: Twenty-seven articles were ultimately included, with one randomized controlled trial and 26 observational studies. A total of 6568 patients were included. Meta-analysis showed that robotic surgery had less estimated blood loss ( < 0.001), blood transfusion ( = 0.04), intraoperative complications ( = 0.001), and conversion to open surgery ( = 0.001), and a shorter hospital stay ( = 0.001), but had a longer operation time ( = 0.04) in surgical staging of endometrial cancer compared with laparoscopy. There were no significant differences in postoperative complications, the total number of lymph nodes harvested, the number of pelvic lymph nodes harvested, and the number of para-aortic lymph nodes harvested between techniques. Robotic surgery had a longer operation time ( = 0.008), less estimated blood loss ( < 0.001), blood transfusion ( < 0.001), and postoperative complications ( < 0.001), and a shorter hospital stay ( < 0.001) compared with laparotomy. There were no significant differences in other variables between techniques.

Conclusion: Robotic surgery is a safer surgical approach than laparoscopy and laparotomy in surgical staging of endometrial cancer, with less estimated blood loss, blood transfusion, and conversion, and the same number of lymph nodes harvested.
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http://dx.doi.org/10.1155/2020/2503753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212337PMC
April 2021

MicroRNA-155 Suppresses the Translation of p38 and Impairs the Functioning of Dendritic Cells in Endometrial Cancer Mice.

Cancer Manag Res 2020 30;12:2993-3002. Epub 2020 Apr 30.

Department of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, People's Republic of China.

Background: Dendritic cells (DCs) are reported to play an important role in activating the anti-tumor immune responses. p38 MAPK14 signaling plays an important role in controlling their activity. Here, we identified that miR-155 suppressed the translation of p38 and impaired the functioning of dendritic cells in endometrial cancer.

Methods: HEC1A endometrial cancer cell lines were used for the study which was transfected in the C57BL/6 mice. Murine bone marrow-derived dendritic cells (BMDCs) were isolated from the mice. Target prediction was done by TargetScan which was confirmed by RT-PCR analysis. The protein expression was carried by Western blot analysis. Levels of IL-12 were evaluated by ELISA. Mice injected with HEC1A cells were subjected to tumor challenge study.

Results: On screening the binding sites of p38 MAPK14 gene, miR-155 was found to bind the 3'UTR directly and blocked its translation. The levels of miR-155 were upregulated in dendritic cells and RAW264.7 cells, miR-155 showed inhibitory effect on expression levels of p38. In dendritic cells, miR-155 was found to regulate the expression of IL-12, also miR-155 inhibitor stimulated the differentiation of Th1 cells in mice induced with endometrial cancer. In dendritic cells, miR-155 inhibited the expression of p38 gene and decreased their ability to interfere in tumor growth.

Conclusion: The study concludes suppressive role of miR-155 in the process of dendritic cells mediated anti-tumor immunity, also inhibiting miR-155 provides a novel strategy for countering endometrial cancer.
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http://dx.doi.org/10.2147/CMAR.S240926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198441PMC
April 2020

Construction and Validation of Nomograms for Predicting the Prognosis of Uterine Leiomyosarcoma: A Population-Based Study.

Med Sci Monit 2020 Apr 9;26:e922739. Epub 2020 Apr 9.

Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).

BACKGROUND Uterine leiomyosarcoma (uLMS) is a rare female malignancy with poor survival rates. The objective of this study was to construct prognostic nomograms for predicting the prognosis of women with uLMS. MATERIAL AND METHODS Patients with uLMS diagnosed between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The essential clinical predictors were identified via univariate and multivariate Cox analysis models. Nomograms were constructed to predict the 3- and 5-year cancer-specific survival (CSS) and overall survival (OS) rates. Concordance index (C-index) and calibration plots were constructed to validate the predictive performance of nomograms. RESULTS We enrolled 1448 patients with uLMS from the SEER database, with 1016 categorized into a training set and 432 categorized into a validation set. In multivariate analysis of the training set, predictors including age, disease stage, histological grade, tumor size, and surgery type were found to be associated with OS and CSS. Race and chemotherapy were only associated with OS. Construction of nomograms based on these predictors was performed to evaluate the prognosis of uLMS patients. The C-index and calibration curves also showed the satisfactory performance of these nomograms for prediction of prognosis. CONCLUSIONS The developed nomograms are useful tools for precisely analyzing the prognosis of uLMS patients, which could help clinicians in making personalized survival predictions and assessing individualized clinical options.
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http://dx.doi.org/10.12659/MSM.922739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170014PMC
April 2020

A Review of IGF1 Signaling and IGF1-related Long Noncoding RNAs in Chemoresistance of Cancer.

Authors:
Li Liu Xiaomao Li

Curr Cancer Drug Targets 2020 ;20(5):325-334

Department of Gynecology and Obstetrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Cancer is still a serious public issue that humans face. Chemoresistance is one of the most important reasons for relapse and poor prognosis. The accumulated data support that the polymorphisms in IGF1 are correlated with both circulating IGF1 levels and cancer risk and activation of IGF1signaling enhances the progression of cancer. Here, we emphasize the role of IGF1 in resistance to various chemotherapies. Dysregulation of IGF1-related lncRNAs may also play an important role in the regulation of chemoresistance by IGF1. Finally, targeting the IGF1 pathway and lncRNAs is effective for increasing the sensitivity of cancer cells to chemotherapies. More basic and clinical studies need to be conducted to investigate the value of targeting IGF1 and IGF1-related lncRNAs in restoring sensitivity to chemotherapies.
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http://dx.doi.org/10.2174/1568009620666200228123754DOI Listing
January 2020

Recurrence-Associated Multi-RNA Signature to Predict Disease-Free Survival for Ovarian Cancer Patients.

Biomed Res Int 2020 14;2020:1618527. Epub 2020 Feb 14.

Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.

Ovarian cancer (OvCa) is an intractable gynecological malignancy due to the high recurrence rate. Several molecular biomarkers have been previously screened for early identifying patients with a high recurrence risk and poor prognosis. However, all the known studies focused on a single type of RNAs, not integrating various types. This study was to construct a new multi-RNA-based model to predict the recurrence and prognosis for OvCa patients by using the messenger RNA (mRNA, including long noncoding RNA (lncRNA)) and microRNA (miRNA) sequencing data of The Cancer Genome Atlas database. After univariate Cox regression and least absolute shrinkage and selection operator analyses, a multi-RNA-based signature (2 miRNAs: hsa-miR-508, hsa-miR-506; 1 lncRNA: TM4SF1-AS1; 11 mRNAs: MAGI3, SLAMF7, GLI2, PDK1, ARID3A, PLEKHG4B, TNFAIP8L3, C1QTNF3, NDUFAF1, CH25H, TMEM129) was generated and used to establish a risk score model. The high- and low-risk patients classified by the median risk score exhibited significantly different recurrence risks (89% versus 61%, < 0.001) and survival time (the area under the receiver operating characteristic curve (AUC) = 0.901 for 5-year disease-free survival (DFS)). This risk model was independent of other clinical features and superior to pathologic staging for DFS prediction (AUC, 0.906 versus 0.524; C-index, 0.633 versus 0.510). Furthermore, some new interaction axes were revealed to explain the possible functions of these RNAs (competing endogenous RNA: TM4SF1-AS1-miR-186-STEAP2, LINC00536-miR-508-STEAP2, LINC00475-miR-506-TMEM129; coexpression: LINC00598-PLEKHG4B). In conclusion, this multi-RNA-based risk model may be clinically useful to stratify OvCa patients with different recurrence risks and survival outcomes and included RNAs may be potential therapeutic targets.
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http://dx.doi.org/10.1155/2020/1618527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044477PMC
December 2020

Ultra pH-sensitive polymeric nanovesicles co-deliver doxorubicin and navitoclax for synergetic therapy of endometrial carcinoma.

Biomater Sci 2020 Apr;8(8):2264-2273

Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

Endometrial carcinoma is a kind of epithelial malignant tumor occurring in the endometrium with high incidence (nearly 200 000 people are diagnosed every year). At present, surgery is the main strategy for the treatment of endometrial carcinoma. However, in special cases such as serous, clear cell carcinoma and postoperative recurrences, chemotherapy is still essential and indispensable. The combined chemotherapy schemes of cisplatin, paclitaxel and doxorubicin (DOX) in clinical applications are unfortunately complicated and easily cause severe side effects. In recent years, with the development of nanotechnology, the targeted delivery of multi-chemotherapeutic drugs shows great advantages in reducing side effects and improving anticancer efficacy. Here, an ultra pH-sensitive nanovesicle based on polyethylene glycol-poly(diisopropylamino)ethyl methacrylate (PEG-PDPA) was fabricated. A chemotherapeutic drug (doxorubicin) and an anti-apoptotic Bcl-2 inhibitor (navitoclax) were co-encapsulated in the hydrophilic cavity and hydrophobic membrane of the vesicle, respectively. After accumulating in the tumor tissue via the enhanced permeability and retention (EPR) effect, the nanovesicles could be efficiently diffused in tumor cells by endocytosis and then rapidly release drugs in response to the lysosomal acidic environment, leading to an enhanced tumor-killing effect based on the combination therapy between DOX and the Bcl-2 inhibitor. The drug co-delivery system and microenvironment-triggered drug release may provide an efficient strategy for endometrial carcinoma therapy.
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http://dx.doi.org/10.1039/d0bm00112kDOI Listing
April 2020

Identification of prognostic immune-related genes in the tumor microenvironment of endometrial cancer.

Aging (Albany NY) 2020 02 19;12(4):3371-3387. Epub 2020 Feb 19.

Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China.

Endometrial cancer (EC) is one of the most common gynecologic malignancies. To identify potential prognostic biomarkers for EC, we analyzed the relationship between the EC tumor microenvironment and gene expression profiles. Using the ESTIMATE R tool, we found that immune and stromal scores correlated with clinical data and the prognosis of EC patients. Based on the immune and stromal scores, 387 intersection differentially expressed genes were identified. Eight immune-related genes were then identified using two machine learning algorithms. Functional enrichment analysis revealed that these genes were mainly associated with T cell activation and response. Kaplan-Meier survival analysis showed that expression of TMEM150B, CACNA2D2, TRPM5, NOL4, CTSW, and SIGLEC1 significantly correlated with overall survival times of EC patients. In addition, using the TIMER algorithm, we found that expression of TMEM150B, SIGLEC1, and CTSW correlated positively with the tumor infiltration levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, and dendritic cells. These findings indicate that the composition of the tumor microenvironment affects the clinical outcomes of EC patients, and suggests that it may provide a basis for development of novel prognostic biomarkers and immunotherapies for EC patients.
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http://dx.doi.org/10.18632/aging.102817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066904PMC
February 2020

New withanolides with anti-inflammatory activity from the leaves of Datura metel L.

Bioorg Chem 2020 01 28;95:103541. Epub 2019 Dec 28.

Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, People's Republic of China. Electronic address:

Twenty three undescribed withanolides, daturmetelides A-W (1-23), were isolated from 70% EtOH extract of the leaves of Datura metel L. The structural characterizations and relative configurations of 1-23 were elucidated by extensive spectroscopic analysis as well as by comparison with literature values. The absolute configurations of 1 and 3 were determined by X-ray crystallography. Bioassay results showed that 1 and 7 exhibited moderate inhibitory effects against NO production in lipopolysaccharide-stimulated RAW 264.7 cells (IC values of 13.74 μM and 13.92 μM, respectively). In addition, 1 and 7 showed significant anti-inflammatory activities against the production of TNF-α, IL-1β, IL-6 and COX-2. Western blot analysis was further performed to reveal the mechanism of anti-inflammatory action via inhibition of the NF-κB activation.
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http://dx.doi.org/10.1016/j.bioorg.2019.103541DOI Listing
January 2020

Expression Profiles of the Phosphatase and Tensin Homolog (PTEN), CDH1, and CDH2 Genes, and the Cell Membrane Protein, CD133, in the Ishikawa Human Endometrial Adenocarcinoma Cell Line.

Med Sci Monit 2019 Dec 21;25:9829-9835. Epub 2019 Dec 21.

Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).

BACKGROUND This study aimed to investigate the expression profile of the phosphatase and tensin homolog (PTEN) gene, the cadherin genes, CDH1 and CDH2, and the cell membrane glycoprotein, CD133, in the Ishikawa human endometrial adenocarcinoma cell line. MATERIAL AND METHODS The Ishikawa endometrial carcinoma cell groups included cells transfected with the pLVX-puro lentiviral expression vector (the Ishikawa-puro group) and cells transfected with the pLVX-puro-PTEN lentiviral expression vector (the Ishikawa-PTEN group). The mRNA expression of the cadherin genes, CDH1 and CDH2, was detected by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). The expression levels of the transmembrane glycoprotein CD133, a cancer stem cell marker, was detected by flow cytometry. RESULTS The expression of CDH1 and CDH2 mRNA in the Ishikawa-PTEN cells was lower than in the control cells. CD133 expression was lower in the Ishikawa-PTEN cells compared with the control cells. CONCLUSIONS This in vitro study showed that in Ishikawa endometrial carcinoma cells, downregulation of PTEN was associated with the expression of the CDH1 and CDH2 genes and upregulated expression of the cell membrane glycoprotein, CD133, which are associated with epithelial-mesenchymal transition (EMT) in malignancy. These findings support the need for further studies to investigate the potential role of PTEN in invasion and metastasis in endometrial carcinoma.
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http://dx.doi.org/10.12659/MSM.918787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937906PMC
December 2019

Prognostic value of metabolic tumor volume and total lesion glycolysis from ¹⁸F-FDG PET/CT in lymph node metastases and risk stratification of endometrial carcinoma.

J Gynecol Oncol 2019 Nov;30(6):e89

Department of Nuclear Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Objective: To investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), measured by preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT), in risk stratification of patients with endometrial carcinoma (EC).

Methods: The patients with pathological diagnosis of EC who underwent preoperative ¹⁸F-FDG PET/CT imaging were retrospectively selected for analysis of the prognostic values of PET parameters in risk classification and lymph node metastases (LNMs). Receiver-operating-characteristic analysis was used to analyze the correlation of PET parameters cutoff values with deep myometrial invasion (MI), lymphovascular space involvement and LNM for prognostic values in risk stratification.

Results: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detection of LNM are 83.3%, 99.7%, 90.9%, 99.5% and 99.2%, respectively. The MTV and TLG of primary lesion of EC in the patients with LNM are notably higher than those in patients without LNM, p<0.010. The MTV and TLG of the EC primary lesions in high-risk patients are significantly higher than those in low-risk patients (p<0.010), but the maximum standardized uptake value (SUVmax) is not. The MTV and TLG of primary lesions were superior to SUVmax for predicting of deep MI, LNM and high-risk of EC (p<0.005).

Conclusion: MTV and TLG of primary lesions are more valuable in predicting risk stratification of EC patients. Preoperative ¹⁸F-FDG PET/CT imaging is useful in predicting the LNM of EC and may help guide pelvic lymphadenectomy to avoid unnecessary pelvic lymphadenectomy in EC patients with low-risk stratification.
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http://dx.doi.org/10.3802/jgo.2019.30.e89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779626PMC
November 2019

Therapeutic effect of human umbilical cord mesenchymal stem cells on tubal factor infertility using a chronic salpingitis murine model.

Arch Gynecol Obstet 2019 08 12;300(2):421-429. Epub 2019 Jun 12.

Department of Obstetrics and Gynecology, Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, China.

Background: The study was conducted to evaluate the application of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of tubal factor infertility (TFI) caused by Chlamydia trachomatis, and investigate their effect on fertility in animal models of chronic salpingitis.

Methods: In this study, we investigated the therapy effects of the transplantation of hUCMSCs in tubal factor infertility using a chronic salpingitis murine model which induced Chlamydia trachomatis. Twenty rats were divided into two groups: control group (n = 10) and treatment group (n = 10). hUCMSCs were given to mice after exposure to C. trachomatis for 4 weeks. After treatment for 4 weeks, five mice were randomly selected from each of the two groups to sacrifice and we examined the organ morphology and pathology, inflammatory cytokines, proliferation, and apoptosis in fallopian tube (FT).The remaining five mice from each group were caged 2:1 with male mice for another 4 weeks, the numbers of pregnant mice and the mean number of pups in the different groups were enumerated and calculated.

Results: Intravaginal inoculation of hUCMSCs alleviated hydrosalpinx of the oviduct. EdU-labeled hUCMSCs are located at the interstitial site of the fallopian tube. Macrophage (F4/80) infiltration was significantly reduced in the treatment group compared with the control group and expression levels of the anti-inflammatory cytokine IL10 were increased after hUCMSCs treatment. Furthermore, mRNA and protein expression levels of PCNA and Caspase-3 were increased and decreased, respectively, in the hUCMSCs' treatment group compared with the control. Moreover, hUCMSCs' transplantation improved murine fertility.

Conclusions: Anti-inflammatory and anti-apoptotic effects of hUCMSCs may play an important role in TFI. Our data suggest that hUCMSCs' transplantation contributed to the repair of tubal injury and improvement of fertility, providing a basis for assessing the contribution of stem cells in the oviduct for direct repair of the tube to assist reproduction.
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http://dx.doi.org/10.1007/s00404-019-05209-6DOI Listing
August 2019

Physicochemical properties and laxative effects of polysaccharides from Anemarrhena asphodeloides Bge. in loperamide-induced rats.

J Ethnopharmacol 2019 Aug 15;240:111961. Epub 2019 May 15.

Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin, 150040, China. Electronic address:

Ethnopharmacological Relevance: As a traditional Chinese herbal medicine, Anemarrhena asphodeloides Bge. possesses the effects of nourishing yin, moistening dryness, clearing lungs and relieving fire. Simultaneously, it has been used to treat constipation for more than one thousand years in China. However, modern medical studies are limited and lacking on its therapeutic mechanism.

Aim Of The Study: This current study was aimed to investigate the laxative activities and explore the potential mechanism of Anemarrhena asphodeloides Bge. polysaccharides (AABP) in loperamide-induced constipation rats.

Materials And Methods: The structure of AABP was determined by using infrared spectrum, high performance gel permeation chromatography (HPGPC), and high performance liquid chromatography (HPLC). Real-time quantitative polymerase chain reaction (PCR), multitudinous methods were adopted to explore the underlining therapeutic mechanism of AABP in treating constipation, including enzyme-linked immunosorbent assay (ELISA), histopathological, immunohistochemistry and western blotting.

Results: In the present study, the average molecular weight of AABP was determined as 1.11 × 10 kDa. The primary monosaccharide compositions were analyzed including D-mannose, L-rhamnose, D-galacturonic acid, D-glucose, D-galactose and L-arabinose (1, 0.04, 0.53, 0.11, 0.33, 0.25, respectively) by high-performance liquid chromatography (HPLC). AABP significantly increased the levels of gastrin (Gas), motilin (MTL), substance P (SP), 5-hydroxytryptamine (5-HT) and vasoactive intestinal peptide (VIP), and decreased the NO content of loperamide-induced rats to ameliorate constipation in the rats. Whilst, AABP repaired the damaged colons by regulating PCNA and ICAM-1 protein expressions. Additionally, AABP up-regulated the levels of SCF, c-Kit, AQP3 and VIP as well as down-regulated the expressions of AQP8, AQP4 and PGE2.

Conclusion: The present findings suggested that AABP were the laxative active ingredients isolated from Anemarrhena asphodeloides Bge., which could treat constipation through regulating the gastrointestinal hormones and neurotransmitters to improve the intestinal motility and water metabolism.
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http://dx.doi.org/10.1016/j.jep.2019.111961DOI Listing
August 2019

iTRAQ-Based Proteomics to Reveal the Mechanism of Hypothalamus in Kidney-Yin Deficiency Rats Induced by Levothyroxine.

Evid Based Complement Alternat Med 2019 4;2019:3703596. Epub 2019 Mar 4.

Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin 150040, China.

Kidney-yin deficiency syndrome (KYDS) is a typical syndrome encountered in traditional Chinese medicine (TCM) and is characterized by impaired lipid and glucose homeostasis. The hypothalamus acts as an important regulatory organ by controlling lipid and glucose metabolism in the body. Therefore, proteins in the hypothalamus could play important roles in KYDS development; however, the mechanisms responsible for KYDS remain unclear. Herein, iTRAQ-based proteomics was performed to analyze the protein expression in the hypothalamus of KYDS rats induced by levothyroxine (L-T). Results revealed a total of 44 downregulated and 18 upregulated proteins in KYDS group relative to the control group. Gene Ontology (GO) analysis revealed that the differently expressed proteins (DEPs) were related to single-organism metabolism process under the biological process (BP), extracellular region part and organelle under the cellular component (CC), and oxidoreductase activity under the molecular function (MF). Kyoto Encyclopedia of Gene and Genomes (KEGG) analysis showed that fatty acid degradation and pyruvate metabolism participated in the metabolism regulation in KYDS rats. RT-PCR validation of five distinctly expressed proteins related to the two pathways was consistent with the results of proteomics analysis. Taken together, the inhibition of fatty acid degradation and pyruvate metabolism in hypothalamus could potentially cause the dysfunction of the lipid and glucose metabolism in KYDS rats. This current study identified some novel potential biomarkers of KYDS and provided the basis for further research of KYDS.
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http://dx.doi.org/10.1155/2019/3703596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425355PMC
March 2019

MicroRNA-433 inhibits cervical cancer progression by directly targeting metadherin to regulate the AKT and β-catenin signalling pathways.

Oncol Rep 2017 Dec 20;38(6):3639-3649. Epub 2017 Oct 20.

Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.

Cervical cancer is one of the most common female malignancies worldwide. Emerging data have shown that microRNAs (miRNAs) play significant roles in various human cancers, including cervical cancer. Aberrantly expressed miRNAs in cervical cancer contribute to tumour occurrence and development as either tumour suppressors or promoters. Research suggests that miRNA-433 (miR-433) possibly plays an important role in the development of various cancer types. However, no study has explored the expression patterns, roles and underlying mechanisms of miR-433 in cervical cancer. In the present study, we demonstrated significant downregulation of miR-433 in cervical cancer tissues and cell lines. Low miR-433 expression was found to significantly correlate with patient characteristics including tumour size, International Federation of Gynecology and Obstetrics stage, lymph node and distant metastases. Functional studies showed that restoration of miR-433 inhibited cell proliferation and invasion and increased apoptosis in cervical cancer cells. Metadherin (MTDH) was also validated as a direct target gene of miR-433. MTDH mRNA expression was upregulated in cervical cancer tissues and was inversely correlated with miR-433 expression. MTDH knockdown showed similar tumour-suppressive roles as miR-433 overexpression in regards to cervical cancer cell proliferation, invasion and apoptosis. Rescue experiments revealed that MTDH overexpression markedly reversed the effects of miR-433 overexpression in regards to proliferation, invasion and apoptosis of cervical cancer cells. Further investigations revealed that miR-433 inactivated AKT and β-catenin pathways in cervical cancer. Collectively, these findings indicate the essential roles of miR-433 in suppressing cervical cancer progression and suggest its potential as a therapeutic target for the treatment of cervical cancer.
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http://dx.doi.org/10.3892/or.2017.6049DOI Listing
December 2017

Mammalian target of rapamycin inhibitor RAD001 sensitizes endometrial cancer cells to paclitaxel-induced apoptosis via the induction of autophagy.

Oncol Lett 2016 Dec 2;12(6):5029-5035. Epub 2016 Nov 2.

Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510089, P.R. China.

The aim of the present study was to investigate the effects of the mammalian target of rapamycin (mTOR) inhibitor, RAD001, on the growth of human endometrial cancer cells. The effects of RAD001 on human endometrial cancer Ishikawa and HEC-1A cell proliferation were determined by MTT assay. Green fluorescent protein microtubule-associated protein 1 light chain 3α (GFP-LC3) protein aggregates were observed under a confocal microscope, and Ishikawa and HEC-1A cell apoptosis was detected using flow cytometry. The expression levels of LC3-I, LC3-II and mTOR proteins were detected by western blot analysis. The results showed that RAD001 effectively inhibited human endometrial cancer Ishikawa and HEC-1A cell proliferation via downregulation of AKT/mTOR phosphorylation. Moreover, RAD001 induced autophagic cell death and a higher sensitivity to paclitaxel-induced apoptosis. These results indicate that RAD001 could have therapeutic potential in human endometrial cancer with hyperactivated AKT/mTOR signaling.
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http://dx.doi.org/10.3892/ol.2016.5338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228433PMC
December 2016

Exenatide inhibits the growth of endometrial cancer Ishikawa xenografts in nude mice.

Oncol Rep 2016 Mar 8;35(3):1340-8. Epub 2015 Dec 8.

Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China.

Studies have showed that diabetes is one of the high risk factors of endometrial cancer; however, no reports describe the anti- or pro-cancer effect of a new kind of anti-diabetes drug, glucagon-like peptide-1 receptor agonist exenatide (exendin-4), on endometrial cancer. To investigate whether exenatide promotes or inhibits the growth of endometrial cancer, we used the subcutaneous human endometrial cancer cell Ishikawa xenografts in nude mouse model, and divided them into control group and exenatide-treated group. The tumor growth rate in exenatide group was slower than that in control group, and the apoptosis rate of exenatide group was higher than that in control group. In vitro, exendin-4 also attenuated Ishikawa cell viability and clone formation rate, but promoted cell apoptosis. There was an increase of phosphorylated-AMPK protein, a decrease of phosphorylated-mTOR protein both in vivo and in vitro after exenatide or exendin-4 treatment. Moreover, when treated with exendin-4 plus AICAR, an AMPK activator, cell apoptosis increased with higher ratio of phosphorylayed-AMPK/AMPK, lower ratio of phosphorylated-mTOR/mTOR and higher expression of cleaved caspase-3 than those in exendin-4 alone group, and the results were the opposite when treated with exendin-4 plus compound C, an AMPK inhibitor. Our results suggest that exenatide could attenuate the growth of endometrial cancer Ishikawa xenografts in nude mice, and AMPK may be the target of the mechanism.
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http://dx.doi.org/10.3892/or.2015.4476DOI Listing
March 2016

Oscope identifies oscillatory genes in unsynchronized single-cell RNA-seq experiments.

Nat Methods 2015 Oct 24;12(10):947-950. Epub 2015 Aug 24.

Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA.

Oscillatory gene expression is fundamental to development, but technologies for monitoring expression oscillations are limited. We have developed a statistical approach called Oscope to identify and characterize the transcriptional dynamics of oscillating genes in single-cell RNA-seq data from an unsynchronized cell population. Applying Oscope to a number of data sets, we demonstrated its utility and also identified a potential artifact in the Fluidigm C1 platform.
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http://dx.doi.org/10.1038/nmeth.3549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589503PMC
October 2015

[Value of hysteroscopy and dilatation and curettage in diagnosis of endometrial cancer].

Zhonghua Fu Chan Ke Za Zhi 2015 Feb;50(2):120-4

Department of Gynecology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.

Objective: To evaluated the value of hysteroscopy and dilatation and curettage (DC) in diagnosis of endometrial cancer.

Methods: This retrospective analysis included clinical pathologic data of 3 676 patients with endometrial cancer from Jan. 1, 2000 to Dec. 31, 2010 in hospitals of endometrial cancer prevention projects in Guangdong Province.

Results: A total of 3 676 patients with endometrial cancer were divided into DC group (3 211 patients) and hysteroscopy group (465 patients). Compared to the results of pathological diagnosis, the accuracy rate between DC group and in hysteroscopy group were no statistically difference was 91.00% (2 922/3 211) vs 90.75% (422/465; χ² = 0.030, P = 0.862). The accuracy rate, sensitivity, specificity, positive predictive value and negative predictive value of cervical involvement between DC group and hysteroscopy group were 81.28% vs 86.45% (P < 0.01), 24.78% vs 23.68% (P > 0.05), 93.76% vs 98.71% (P < 0.01), 46.75% vs 78.26% (P < 0.01) and 84.95% vs 86.88% (P > 0.05), respectively. Rate of positive peritoneal cytology in DC group was 4.76% (153/3 211), and the rate was 3.23% (15/465) in hysteroscopy group, which were no statistically difference (χ² = 2.206, P = 0.137). There were no statistically difference in 5-year overall survival (91.02% vs 92.03%; χ² = 0.033, P = 0.856) and 5-year progression-free survival (89.81% vs 91.83%; χ² = 1.508, P = 0.219) between DC group and hysteroscopy group.

Conclusions: Hysteroscopy and dilatation and curettage is an effective method in diagnosis of endometrial cancer, especially hysteroscopy is better in diagnosis of cervical involvement. Hysteroscopy don't improve risks of positive peritoneal cytology and don't affect the prognosis of patients with endometrial cancer.
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February 2015

Autophagy inhibition enhances sensitivity of endometrial carcinoma cells to paclitaxel.

Int J Oncol 2015 27;46(6):2399-408. Epub 2015 Mar 27.

Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, P.R. China.

Autophagy has been shown to be involved in cancer cell resistance to chemotherapy. Paclitaxel, a widely used chemotherapeutic drug, was demonstrated to induce autophagy in various cancer cells. Therefore, we sought to evaluate the role of autophagy on the paclitaxel-induced cell death in endometrial carcinoma. In this study, we found that paclitaxel induced autophagy in paclitaxel-insensitive HEC-1A and JEC cells, exhibiting an increased microtubule associated protein 1 light chain 3 (LC3)-II/LC3-I ratio, a decrease in p62/SQSTM1 abundance, the upregulation of Beclin 1 expression and punctate dots of yellow fluorescent protein (YFP)-LC3 in the cytosol. Paclitaxel-mediated cell death was further potentiated by pretreatment with autophagy inhibitor chloroquine (CQ) or shRNA against the autophagic gene beclin 1. Moreover, paclitaxel stimulated reactive oxygen species (ROS) generation, and inhibition of the ROS by antioxidant N-acetyl-cysteine (NAC) blocked paclitaxel-induced autophagy, indicating that paclitaxel-induced autophagy in endometrial carcinoma cells is mediated by ROS. These findings suggest that paclitaxel-elicited autophagic response plays a protective role that impedes the eventual death of endometrial carcinoma cell, and that autophagy-inhibitor therapy could be an effective and potent strategy to improve paclitaxel treatment outcomes in the treatment of endometrial carcinoma.
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http://dx.doi.org/10.3892/ijo.2015.2937DOI Listing
January 2016

Ovarian steroid cell tumor, not otherwise specified: A rare case of postmenopausal vaginal bleeding.

Oncol Lett 2014 Sep 13;8(3):1187-1189. Epub 2014 Jun 13.

Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China.

Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS) are particularly rare ovarian tumors, which are composed of steroid-hormone secreting cells. The majority of patients with this tumor produce excessive quantities of testosterone and virilization is common. The current report presents a rare case of SCT in a 59-year-old female who presented with postmenopausal vaginal bleeding. The patient had experienced irregular vaginal bleeding for two months, 12 years after menopause. Transvaginal ultrasound and magnetic resonance imaging identified a solid adnexal mass and the pathological result of diagnostic curettage showed a proliferative endometrium. The patient's serum estrogen and testosterone levels were elevated (393.71 nmol/l and 22.28 nmol/l, respectively). The patient underwent an exploratory laparotomy, hysterectomy and bisalpingectomy. The neoplasm was well-circumscribed, solid, homogeneous and yellow in color. Microscopically, the tumor was predominantly composed of granular eosinophilic or vacuolated cytoplasm. Reinke's crystals, prominent nucleoli and Call-Exner bodies were not observed, and there was no mitotic figure. Immunohistochemistry demonstrated that the tumor cells were strongly positive for inhibin. The present rare case aims to expand the current knowledge of this type of ovarian tumor.
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http://dx.doi.org/10.3892/ol.2014.2251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4114601PMC
September 2014

[Efficacy and safety of a combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20 µg in a 24+4-day regimen in China].

Zhonghua Fu Chan Ke Za Zhi 2014 May;49(5):355-9

Email:

Objective: To assess the efficacy, bleeding pattern, cycle control and safety of a combined oral contraceptive (YAZ) containing drospirenone 3 mg and ethinylestradiol 20 µg in a 24+4-day regimen in China.

Methods: This is a multi-center, open, one-label study. Healthy females aged 18-45 years received YAZ for 13 cycles. Following-ups were scheduled during the treatment phase on Day 12-19 of Cycle 1, 4, 7 and 10 and 10-17 days after completing the study. The efficacy variables were the number of unintended pregnancies, bleeding pattern and cycle control. The safety variables were adverse events (AE), lab examinations, physical and gynecological examinations, vital signs and body weights and questionnaires.

Results: Four pregnancies occurred among 675 women for 603.78 women-years, resulting in a Pearl index (PI) of 0.7 and adjusted PI of 0.6. The cumulative 1-year pregnancy rate was 0.66%. The mean number of bleeding/spotting days was (26.3 ± 12.4) days in reference period 1 and (15.4 ± 5.5) days in reference period 4. 94.2% (582/618)- 96.8% (538/558) subjects experienced scheduled bleeding. The mean duration of scheduled bleeding decreased from (5.9 ± 3.2) to (5.0 ± 1.6) days. The percentage of women with intermenstrual bleeding decreased from 14.5% (90/621) at Cycle 1 to 2.3% (13/558) at Cycle 12. The common AE relating treatment include nausea (3.4%, 23/675), breast tenderness (1.2%, 8/675), dizzy (1.2%), vagina bleeding (1.2%). No serious AE relating treatment occurred. 85.6% (542/633) subjects were satisfied or very satisfied with the study treatment.

Conclusion: YAZ is highly effective, acceptable and safe for Chinese women.
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May 2014

Etoricoxib in the treatment of primary dysmenorrhea in Chinese patients: a randomized controlled trial.

Curr Med Res Opin 2014 Sep 30;30(9):1863-70. Epub 2014 Jun 30.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing , China.

Objective: Assess the efficacy and safety of etoricoxib 120 mg compared with ibuprofen 600 mg qid in the treatment of moderate to severe primary dysmenorrhea in Chinese women.

Methods: This multicenter, double-blind, two-period, cross-over study randomized healthy, Chinese women ≥18 years of age to etoricoxib 120 mg qd or ibuprofen up to 2400 mg (600 mg qid) upon onset of moderate or severe primary dysmenorrhea symptoms during two menstrual cycles. The primary efficacy endpoint was Total Pain Relief score over the first 6 hours (TOPAR6). Secondary endpoints included Sum of Pain Intensity Difference scores over the first 6 hours (SPID6) and Patient's Global Evaluation (GLOBAL) of pain at 6 and 24 hours post initial dose. The primary hypothesis was that etoricoxib would be non-inferior to ibuprofen. Adverse experiences (AE) were monitored and evaluated.

Results: A total of 139 patients were included in this study. Difference in least squares (LS) mean (95% CI) TOPAR6 score for etoricoxib vs. ibuprofen was 0.89 (0.03, 1.76) (p = 0.043). LS mean (95% CI) difference for etoricoxib vs. ibuprofen SPID6, GLOBAL6, and GLOBAL24 were 0.20 (-1.16, 1.57) (p = 0.768), 0.26 (0.07, 0.45) (p = 0.007), and 0.36 (0.17, 0.54) (p < 0.001), respectively. AEs were rare, with the following AEs determined to be drug-related: hypomenorrhea (two patients on etoricoxib) and allergic dermatitis (one patient on ibuprofen). Limitations of the study design include a sample size that is not adequate for evaluation of rare adverse effects, an evaluation period that was limited to 24 hours, and inconsistent frequency of active treatment doses between etoricoxib (once daily) and ibuprofen (up to four times daily).

Conclusions: The primary objective of the study was met, demonstrating that etoricoxib 120 mg qd was non-inferior to ibuprofen 600 mg qid; further, etoricoxib was statistically superior to ibuprofen 600 mg qid according to the primary endpoint (TOPAR6) and patient global assessments of study medication. Etoricoxib and ibuprofen were generally well tolerated.
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http://dx.doi.org/10.1185/03007995.2014.925437DOI Listing
September 2014

Mother-to-child transmission of HBV: review of current clinical management and prevention strategies.

Rev Med Virol 2014 Nov 23;24(6):396-406. Epub 2014 Jun 23.

Department of Obstetrics and Gynecology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Mother-to-child transmission (MTCT) of HBV is responsible for approximately half of the HBV transmission routes and continues to be a challenging problem worldwide. Even after the development of effective vaccines and clear World Health Organization guidelines toward HBV several decades ago, 1-9% newborns of HBV-carrying mothers still acquire HBV in early life as a result of in utero infection. The prevention of MTCT is of high importance, because chronically infected individuals function as a reserve for sustained HBV transmission, and 25% of them can develop asymptomatic liver cirrhosis and hepatocellular carcinoma. In this article, we review the canonical and novel HBV infection routes/mechanisms, influencing factors, diagnostic criteria, and interruption strategies for HBV MTCT. The preventative strategy of HBV MTCT has evolved from routine postpartum HB immune globulin (HBIG) plus HB vaccine schedules to administration of HBIG or nucleoside analogs during pregnancy and minimizing the exposure of maternal body fluids to the newborn during delivery.
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http://dx.doi.org/10.1002/rmv.1801DOI Listing
November 2014
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