Usefulness of human epididymis protein 4 in predicting cytoreductive surgical outcomes for advanced ovarian tubal and peritoneal carcinoma

Objective： Human epididymis protein 4（HE4） is a promising biomarker of epithelial ovarian cancer（EOC）. But its role in assessing the primary optimal debulking（OD） of EOC remains unknown. The purpose of this study is to elucidate the ability of preoperative HE4 in predicting the primary cytoreductive outcomes in advanced EOC, tubal or peritoneal carcinoma.Methods： We reviewed the records of 90 patients with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at the Department of Obstetrics and Gynecology of Peking University People＇s Hospital between November 2005 and October 2010. Preoperative serum HE4 and CA125 levels were detected with EIA kit. A receiver operating characteristic（ROC） curve was used to determine the most useful HE4 cut-off value. Logistic regression analysis was performed to identify significant preoperative clinical characteristics to predict optimal primary cytoreduction.Results： OD was achieved in 47.7%（43/48） of patients. The median preoperative HE4 level for patients with OD vs. suboptimal debulking was 423 and 820 pmol/L, respectively（P〈0.001）. The areas under the ROC curve for HE4 and CA125 were 0.716 and 0.599, respectively（P=0.080）. The most useful HE4 cut-off value was 473 pmol/L. Suboptimal cytoreduction was obtained in 66.7%（38/57） of cases with HE4 ≥473 pmol/L compared with only 27.3%（9/33） of cases with HE4 〈473 pmol/L. At this threshold, the sensitivity, specificity, positive predictive value（PPV） and negative predictive value（NPV） for diagnosing suboptimal debulking were 81%, 56%, 67%, and 73%, respectively. Logistic regression analysis showed that the patients with HE4 ≥473 pmol/L were less likely to achieve OD（odds ratio =5.044, P=0.002）.Conclusions： Preoperative serum HE4 may be helpful to predict whether optimal cytoreductive surgery could be obtained or whether extended cytoreduction would be needed by an interdisciplinary team.

Combined detection and subclass characteristics analysis of CTCs and CTECs by SE-iFISH in ovarian cancer

Objective:Hematogenous metastasis is essential for the progression of ovarian cancer(OC),and circulating tumor cells(CTCs)are part of the metastatic cascade.However,the detection rate of CTC is low due to the use of less sensitive detection methods.Therefore,this study aimed to detect CTCs and circulating tumorigenic endothelial cells(CTECs)in patients with OC using subtraction enrichment and immunostaining and fluorescence in situ hybridization(SE-iFISH).Methods:We enrolled a total of 56 subjects,including 20 OC patients and 36 ovarian benign tumor patients.CTCs and CTECs were captured by subtraction enrichment(SE)and counted and classified according to immunofluorescence staining of tumor markers(TMs)carbohydrate antigen 125(CA125)and human epididymis protein 4(HE4)combined with fluorescence in situ hybridization(iFISH)of chromosome 8(Chr8)aneuploidy.The diagnostic value and subtype characteristics of CTCs and CTECs were investigated.Results:The detection rate of CTCs by SE-iFISH was high.Compared with CA125 and HE4,Chr8 aneuploidy was the major identification feature of CTC.CTC counts in OC were statistically higher than those in benign groups.CTC and CTEC with≥pentaploidy were detected in both groups,illustrating the poor diagnostic value of CTC or CTEC.Distributions of triploid and tetraploid CTC subtypes were significantly different,and combined detection of triploid and tetraploid CTCs showed the best diagnostic value.In contrast,the distribution of CTECs in the OC and benign groups had no statistically significant difference.Small CTCs accounted for over 1/3 of the total CTC count.We also found that small CTCs and CTECs primarily comprised triploid cells,while large CTCs and CTECs mainly comprised pentaploidy and beyond.Conclusions:The application of SE-iFISH offered a more comprehensive understanding of heterogeneous CTCs and CTECs in OC.Analysis of subclass characteristics of the CTCs and CTECs according to Chr8 aneuploidy and cell size may broaden their potential clinical utility and deepen mechanistic studies in OC.

IGHG1 promotes motility likely through epithelial-mesenchymal transition in ovarian cancer

Objective： Ovarian cancer（OC） is one of the leading causes of death for female cancer patients. COC166-9 is an OC-specific monoclonal antibody and we have identified immunoglobulin γ-1 heavy chain constant region（IGHG1） as its antigen. We explore the function of IGHG1 in proliferation, apoptosis and motility of OC cells further in this research.Methods： IGHG1 expression in OC specimens was detected through immunohistochemistry. Real-time quantitative polymerase chain reaction（RT-q PCR） or western blotting assay was used to test IGHG1 expression in OC cells. Viability of OC cells was tested by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT）assay. Flow cytometry or western blotting assay was used to detect cell cycle and apoptosis. Cellular motility was analyzed by using transwell assay and the markers of epithelial-mesenchymal transition（EMT） were tested through immunoblots.Results： Although it exerts negligible effect on the viability and apoptosis of OC cells, IGHG1 could promote migration and invasion of malignant cells in vitro. Mechanistically, IGHG1 increases the expression of N-cadherin and Vimentin while decreases E-cadherin expression. Additionally, IGHG1 expression in OC specimens is higher relative to the paired normal counterparts. Further analysis demonstrates that the increased IGHG1 expression correlates positively with the lymph node metastasis of OC.Conclusions： IGHG1 promotes the motility of OC cells likely through executing the EMT program. Increased IGHG1 expression in OC specimens is associated with the lymph node metastasis.

Evaluation of COC183B2 antibody targeting ovarian cancer by near-infrared fluorescence imaging

Objective: To evaluate the imaging potential of a novel near-infrared(NIR) probe conjugated to COC183 B2 monoclonal antibodies(MAb) in ovarian cancer(OC).Methods: The expression of OC183 B2 antigen in OC was determined by immunohistochemical(IHC) staining using tissue microarrays with the H-score system and immunofluorescence(IF) staining of tumor cell lines.Imaging probes with the NIR fluorescent dye cyanine 7(Cy7) conjugated to COC183 B2 Mab were chemically engineered. OC183 B2-positive human OC cells(SKOV3-Luc) were injected subcutaneously into BALB/c nude mice. Bioluminescent imaging(BLI) was performed to detect tumor location and growth. COC183 B2-Cy7 at 1.1,3.3, 10, or 30 μg were used for in vivo fluorescence imaging, and phosphate-buffered saline(PBS), free Cy7 dye and mouse isotype immunoglobulin G(IgG)-Cy7(delivered at the same doses as COC183 B2-Cy7) were used as controls.Results: The expression of OC183 B2 with a high H-score was more prevalent in OC tissue than fallopian tube(FT) tissue. Among 417 OC patients, the expression of OC183 B2 was significantly correlated with the histological subtype, histological grade, residual tumor size, relapse state and survival status. IF staining demonstrated that COC183 B2 specifically expressed in SKOV3 cells but not HeLa cells. In vivo NIR fluorescence imaging indicated that COC183 B2-Cy7 was mainly distributed in the xenograft and liver with optimal tumor-to-background(T/B)ratios in the xenograft at 30 μg dose. The highest fluorescent signals in the tumor were observed at 96 h postinjection(hpi). Ex vivo fluorescence imaging revealed the fluorescent signals mainly from the tumor and liver. IHC analysis confirmed that xenografts were OC183 B2 positive.Conclusions: COC183 B2 is a good candidate for NIR fluorescence imaging and imaging-guided surgery in OC.

Development of Profitable Phytoremediation of Contaminated Soils with Biofuel Crops

Contamination of agricultural soil has been a worldwide concern, and phytoremediation is a promising alternative to conventional soil clean-up technology as a low cost and environment-friendly technology. However, the field application of phytoremediation is still limited, because of its low efficiency and long-period needed. In this paper, with discussion of the characteristics, mechanisms and development of phytoremediation, we suggested a profitable phytoremediation strategy using biofuel crops for both utilization and remediation of contaminated soil. In this strategy, the owners of contaminated sites possibly cost nothing, but obtain income through selling the biofuel crop for factories produced biofuel, thus the practical application of phytoremediation can be effectively promoted. In order to test the feasibility of the suggested strategy, a hydroponic cultural experiment and a pot experiment were carried out to assess the phytoremediation potential of some biofuel crops. The hydroponic cultural experiment showed that the two biofuel plants, sunflower and maize, had a better or similar accumulation level of Pb, Cu and Cd than the two accumulator plants. The pot cultural experiment showed that wheat and barley with white-rot-fungus inoculation greatly promoted crop biomass, soil microbial population, and dioxins removal efficiency. These results indicate that phytoremediation using biofuel plants possibly works effectively for remediation of contaminated soils as well as provide economic benefits to the owners of contaminated sites. Therefore, biofuel crops would be a reasonable choice for phytoremediation of contaminated soils.

Phytoremediation Potential of Sorghum as a Biofuel Crop and the Enhancement Effects with Microbe Inoculation in Heavy Metal Contaminated Soil

Phytoremediation is an eco-friendly and low-cost biotechnology using plants to extract, contain, degrade, or immobilize pollutants from the contaminated environment. Selection of the ideal plant species and suitable enhancing measures to obtain high remediation efficiency and large valuable biomass are essential requirement for a successful phytoremdaition. Sorghum (Sorghum bicolor L.) is one of the most attractive bioenergy crops for producing biofuels with high biomass production. In this study, the phytoremediation potential of sorghum to heavy metals and the promotion effects by a lead-tolerant fungus (LTF) were investigated using a multiple heavy metal contaminated soil with Pb, Ni, and Cu. The results showed that the sorghum survived the heavy contamination, and LTF inoculation promoted the plant growth and increased the phytoextraction yields of Pb, Ni, and Cu. The phytoextraction potential (μg/plant) of the whole sorghum for Sorghum were 410 (Pb), 74 (Ni), and 73 (Cu), and for Sorghum with LTF inoculation were 590 (Pb), 120 (Ni), and 93 (Cu), respectively. The results suggested that sorghum would be one of the ideal candidates for phytoremediation of contaminated soil because of its high phytoremediation potential, large biomass production, and utilization in biofuel production.

Report of China's innovation increase and research growth in radiation oncology

Aims： To investigate the research status of radiation oncology in China through survey of literature in international radiation oncology journals and retrospectively compare the outputs of radiation oncology articles of the three major regions of China--Mainland （ML）, Taiwan （TW） and Hong Kong （HK）. Methods： Radiation oncology journals were selected from ＂oncology＂ and ＂radiology, nuclear ＆ medical image＂ category from Science Citation Index Expand （SCIE）. Articles from the ML, TW and HK were retrieved from MEDLINE. The number of total articles, clinical trials, case reports, impact factors （IF）, institutions and articles published in each journals were conducted for quantity and quality comparisons. Results： A total 818 articles from 13 radiation oncology journals were searched, of which 427 are from ML, 259 from TW, and 132 from HK. Ninety-seven clinical trials and 5 case reports are reported in China. Accumulated IF of articles from ML （1,417.11） was much higher than that of TW （1,003.093） and HK （544.711）, while the average IF of articles from ML is the lowest. Conclusions： The total number of articles from China especially ML increased significantly in the last decade. The number of articles published from the ML has exceeded those from TW and HK. However, the quality of articles from TW and HK is better than that from ML.

Effects of Agaricus blazei Murill Polysaccharides on Leadinduced Disturbance of Morphology and ASIC1a and ASIC2b Gene Expression in Hippocampus of Rats

The present study was undertaken to investigate the effects of Agaricus blazei murill polysaccharides on morphology of hippocampus tissue and expression of ASIC1a and ASIC2b mRNA in lead-poisoning rats.Forty SD rats were divided into five groups：control group,lead group,experimental group 1,2,3.After 60d of treatments,hippocampus tissues were observed by HE staining and the expression levels of ASIC1a and ASIC2b mRNA were determined by the flouoreescent quantitative real-time polymerase chain reaction（FQRT-PCR）.The results showed that after lead induction,the number of hippocampus neuron increased,cell gap increased,the chromatin was stained lightly;after administration of ABMP,the number of the hippocampus neuron increased as the dose of ABMP rose,cell gap decreased,the chromatin was stained darkly.The expression level of ASIC1a mRNA in hippocampus of rats in ABMP group decreased extremely significantly compared with that in the model group（P〈0.01）.Lead exposure and ABMP exhibited no significant effects on the expression level of ASIC2b mRNA.ABMP possesses a protective effect on nervous system of rats exposed to lead by combining with lead.

Characterization of candidate factors associated with the metastasis and progression of high-grade serous ovarian cancer

Background:High-grade serous ovarian cancer(HGSOC)is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature.This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC.Methods:Transcriptomic data of HGSOC patients’samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas(TCGA)database.Hub genes’immune landscapes were estimated by the Tumor Immune Estimation Resource(TIMER)database.Finally,using 25 HGSOC patients'cancer tissues and 10 normal fallopian tube tissues,immunohistochemistry(IHC)was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics(FIGO)stages.Results:Fourteen DEGs,ADIPOQ,ALPK2,BARX1,CD37,CNR2,COL5A3,FABP4,FAP,GPR68,ITGBL1,MOXD1,PODNL1,SFRP2,and TRAF3IP3,were upregulated in metastatic tumors in every database while CADPS,GATA4,STAR,and TSPAN8 were downregulated.ALPK2,FAP,SFRP2,GATA4,STAR,and TSPAN8 were selected as hub genes significantly associated with survival and recurrence.All hub genes were correlated with tumor microenvironment infiltration,especially cancer-associated fibroblasts and natural killer(NK)cells.Furthermore,the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics(FIGO)stage,and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC(P=0.0002 and P=0.0001,respectively).Conclusions:This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses.We identified six hub genes that were correlated with the progression of HGSOC,particularly FAP and SFRP2,which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.

A Critical Review of Chinese Theoretical Research on Moral Education Since 2000

Purpose:The purpose of this article is to summarize and reflect Chinese theoretical research on moral education in the context of globalization and value pluralism since 2000 and to propose possible directions for the future research.Design/Approach/Methods:The research methods in this article are primarily literature review.Those papers which met the following criteria were selected and included in this review:(1)Papers published from 2000 to 2014 were included if they were cited by at least one other published article and(2)papers published from 2015 to 2017 were included if they were presented in a core research journal.Based on that,speculative thinking and critical thinking are also embodied in this research.Findings:Based on the features of“a man of virtue,”the article identifies the four dimensions that have influenced Chinese thinking about moral education:(1)Kantian and Enlightenment philosophy,(2)emotion and life experience,(3)social rights,and(4)the culture-value dimension.The four dimensions ofmoral education theory are related and complement,rather than contradict,eachother.The author argues that the research scopes underlying current moral education theories are fairly narrow.Amore comprehensive,interdisciplinary approach is needed to improve theoretical research and to enhance the effectiveness of moral education practice in schools and universities.Originality/Value:The article provides a latest overview and critical insights to consolidate the foundation of moral education in an era of societal transformation by comparing moral education research between China and the West and proposing realizing a deep integration between theory and practice.

An experimental study on autologous transplantation of fresh ovarian tissue in sheep

Objective:To investigate current autologous transplantation methods and sites of ovarian tissues in sheep.Methods:Sheep ovaries were resected.Ovarian cortices were sliced and transplanted orthotopically into the ovarian mesangial latum and heterotopically into the greater omentum and under groin skin.The grafts were removed two months after transplantation and examined to evaluate the survival of follicles(hematoxylin-eosin staining)and help determining feasible graft sites and transplantation methods.Results:Graft nodules were found in the transplanted sites.HE staining of the grafts showed that multiple primordial follicles were able to survive in the grafts on both sides of the ovarian mesangial latum,the right side of the greater omentum,and the left inguinal subcutaneous tissue.Secondary or cystic follicles were found in almost all of the grafts.Conclusion:The ovarian mesangial latum,the greater omentum and the inguinal subcutaneous tissue can be used as autologous transplantation sites,where sheep ovarian tissue can survive and the follicles grow and develop in good condition.

Precise capture of circulating endometrial cells in endometriosis

Background:Endometriosis(EM)is a complex benign gynecological disease,but it has malignant biological behavior and can invade any part of the body.Clinical manifestations include pelvic pain,dysmenorrhea,infertility,pelvic nodules,and masses.Our previous study successfully detected circulating endometrial cells(CECs)in the peripheral blood of patients with EM.The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method,to further accurately capture CECs,understand the characteristics of these cells,and explore the relationship between CECs and the clinical course characteristics of patients with EM.Methods:Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells(CVECs)was taken from EM patients(n=34)hospitalized in the Peking University People’s Hospital.We used the subtraction enrichment and immunostaining fluorescence in situ hybridization(SE-iFISH)method to exclude the interference of red blood cells,white blood cells,and CVECs,so as to accurately capture the CECs in the peripheral blood of patients with EM.Then we clarified the size and ploidy number of chromosome 8 of CECs,and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics.Results:The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH.Overall,34 eligible EM patients were enrolled.The results showed that the detection rates of CECs were 58.8%in EM patients and 16.7%in the control group.However,after classification according to clinical characteristics,more CECs could be detected in the peripheral blood of patients with rapidly progressive EM,with a detection rate of 94.4%(17/18).In total,63.5%(40/63)of these cells were small cells with diameters below 5μm,and 44.4%(28/63)were aneuploid cells.No significant association was found between the number of CECs and EM stage.Conclusion:The number and characteristics of CECs are related to the clinical course characteristics of patients with EM,such as pain and changes in lesion size,and may be used as biomarkers for personalized treatment and management of EM in the future.