Search

The clinical heterogeneity of early-stage endometrial cancer (EC) is worthy of further study to identify high-quality prognostic markers and their potential role in aggressive tumor behavior. Mutation of TP53 was considered as an important primary triage in modified molecular typing for EC, it still cannot precisely predict the prognosis of EC. After proteomic analysis of cancer and para-cancerous tissues from 24 early-stage endometrioid EC patients with different survival outcomes, 13 differentially expressed proteins were screen out while 2 proteins enriched in p53 signaling pathway were further identified by single-cell transcriptome (scRNA-seq). Interestingly, tumor necrosis factor type-1 receptor-associated protein (TRAP1) and calmodulin-regulated spectrin-associated protein family member 3 (CAMSAP3) were found to be significantly downregulated in the specific cell cluster. Expectedly, the signature genes of TRAP1low/CAMSAP3low cluster included classical oncogenes. Moreover, close cellular interactions were observed between myeloid cells and the TRAP1low/CAMSAP3low cluster after systematically elucidating their relationship with tumor microenvironment (TME). The expression of TRAP1 and CAMSAP3 was verified by immunohistochemistry. Thus, a novel prediction model combining TRAP1, CAMSAP3 and TP53 was construct by multi-omics. Compared with the area under the curve, it demonstrated a significantly improvemrnt in the diagnostic efficacy in EC patients from TCGA bank. In conclusion, this work improved the current knowledge regarding the prognosis of early-stage EC through proteomics and scRNA-seq. These findings may lead to improvements in precise risk stratification of early-stage EC patients. [ABSTRACT FROM AUTHOR]

This study introduced a novel subtype classification method for endometrial cancer (EC) with mismatch repair deficiency (MMRd) by employing immune status and prognosis as the foundational criteria. The goal was to enhance treatment guidance through precise subtype delineation. Methods: Study Cohort: This study encompassed a cohort of 119 patients diagnosed with MMRd-EC between 2015 and 2022. Analyses using t-tests and Mann–Whitney U-tests were performed to assess prognostic markers and peripheral blood immune cell profiles in patients with MutS deficiency (MutS-d) versus those with MutL deficiency (MutL-d). Logistic regression analysis was used to identify independent risk factors. Bioinformatics Analysis: An online database was used to assess the prognostic implications, immune cell infiltration, and immune checkpoint involvement associated with the deficiency of MutS versus MutL in EC. Results: Patients with MutL-d exhibited heightened risk factors, including elevated cancer grade and increased myometrial invasion, leading to poorer prognosis and shorter overall survival and progression-free survival. Regarding systemic immune status, patients with MutL-d demonstrated decreased peripheral blood lymphocyte percentage, lymphocyte count, and CD8+ T cell percentage. For local immunity, the infiltration of natural killer cells, CD8+ T cells, and cytotoxic T lymphocytes in the tumor tissue was reduced in patients with MutL-d. Additionally, patients with MutL-d exhibited lower expression of immune checkpoint markers. The composition of immune subtypes and survival outcomes also indicate that patients with MutL-d have a poorer immune status and prognosis than the patients with MutS-d. Conclusion: Patients with MMRd-EC can be subclassified according to MutS or MutL deficiency. Patients with MutS-d exhibited better immune status, prognosis, and immunotherapy benefits than those with MutL-d. These results can help guide patients to a more precise treatment. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health issue closely associated with multiple extrahepatic cancers. The association between MAFLD and clinical outcomes of endometrial cancer (EC) remains unknown. Methods: We retrospectively included 725 EC patients between January 2012 and December 2020. The odds ratios (ORs) were calculated using logistic regression analyses. Kaplan–Meier survival curves were used for survival analysis. Results: Among EC patients, the prevalence of MAFLD was 27.7% (201/725, 95% confidence interval (Cl) = 0.245–0.311). MAFLD was significantly associated with cervical stromal involvement (CSI) (OR = 1.974, 95% confidence interval (Cl) = 1.065–3.659, p = 0.031). There was a significant correlation between overall survival (OS) and CSI (HR = 0.31; 95%CI: 0.12–0.83; p = 0.020), while patients with MAFLD had a similar OS to those without MAFLD (p = 0.952). Moreover, MAFLD was significantly associated with CSI in the type I EC subgroup (OR = 2.092, 95% confidence interval (Cl) = 1.060–4.129, p = 0.033), but not in the type II EC subgroup (p = 0.838). Further logistic regression analysis suggested that the hepatic steatosis index (HSI) was significantly associated with CSI among type I EC patients without type 2 diabetes mellitus (T2DM) (OR = 1.079, 95% confidence interval (Cl) = 1.020–1.139, p = 0.012). Conclusions: About one-quarter of our cohort had MAFLD. MAFLD was associated with the risk of CSI in EC patients, and this association existed in type I EC patients but not in type II EC patients. Furthermore, the HSI can help predict CSI in type I EC patients without T2DM. [ABSTRACT FROM AUTHOR]

Estrogen-related receptor alpha (ERRα) plays an important role in endometrial cancer (EC) progression. However, the biological roles of ERRα in EC invasion and metastasis are not clear. This study aimed to investigate the role of ERRα and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) in regulating intracellular cholesterol metabolism to promote EC progression. ERRα and HMGCS1 interactions were detected by co-immunoprecipitation, and the effects of ERRα/HMGCS1 on the metastasis of EC were investigated by wound-healing and transwell chamber invasion assays. Cellular cholesterol content was measured to verify the relationship between ERRα and cellular cholesterol metabolism. Additionally, immunohistochemistry was performed to confirm that ERRα and HMGCS1 were related to EC progression. Furthermore, the mechanism was investigated using loss-of-function and gain-of-function assays or treatment with simvastatin. High expression levels of ERRα and HMGCS1 promoted intracellular cholesterol metabolism for invadopodia formation. Moreover, inhibiting ERRα and HMGCS1 expression significantly weakened the malignant progression of EC in vitro and in vivo. Our functional analysis showed that ERRα promoted EC invasion and metastasis through the HMGCS1-mediated intracellular cholesterol metabolism pathway, which was dependent on the epithelial–mesenchymal transition pathway. Our findings suggest that ERRα and HMGCS1 are potential targets to suppress EC progression. [ABSTRACT FROM AUTHOR]

There is evidence that coinfection of cervicovaginal high‐risk human papillomavirus (HR‐HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR‐HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR‐HPV infection in women aged 20–45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20–45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR‐HPV genotyping and cervical cytology were performed at each follow‐up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C‐myc, TLR4, NF‐κB, and hTERT quantification. A total of 920 women were included. The abundance of Prevotella (p = 0.016) and Gardnerella (p = 0.027) were higher, whereas the abundance of Lactobacillus was lower (p = 0.001) in women with persistent HR‐HPV infection and high‐grade squamous intraepithelial lesions (HSIL). The abundance of Prevotella (p = 0.025) and Gardnerella (p = 0.018) increased in the vaginas of women with persistent HPV16 infection, whereas only the abundance of Prevotella (p = 0.026) was increased in women with persistent HPV18 infection. The abundance of Prevotella in the vagina was significantly positively correlated with the expression levels of TLR4, NF‐κB, C‐myc, and hTERT in host cervical cells (p < 0.05). Our findings suggest that overgrowth of Prevotella in the vagina may influence the occurrence of persistent HR‐HPV infection‐related cervical lesions through host NF‐κB and C‐myc signaling. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore lymphocyte subsets for the personalized prediction of endometrioid endometrial cancer (EEC) risk and evaluated the correlation between immune cells and International Federation of Gynecology and Obstetrics (FIGO) staging in patients with EEC. Patients and Methods: A case-control study was conducted to analyze the clinical data of 421 patients admitted to Fujian Maternity and Child Health Hospital from October 2017 to December 2021. t-tests or Mann–Whitney U-tests were used to analyze the percentages and absolute counts of peripheral blood lymphocyte subsets in patients with EEC and patients without cancer. The independent risk factors for ECC and FIGO stage were analyzed via multivariate binary logistic regression. The receiver operating characteristic curve was calculated to evaluate the prediction efficacy of risk factors on ECC. Results: The CD4+ T% in the 121 patients with EEC was lower than in the 300 patients without cancer (P = 0.013). The absolute counts of peripheral CD4+ T (P = 0.002) and T cells (P = 0.007) in 37 patients with EEC were lower than in 51 patients without cancer. Multivariate binary logistic regression analysis showed that CD4+ T% and natural killer cell (NK)% were independent risk factors for FIGO staging in patients with EEC. NK% was significantly higher in patients with advanced stage (FIGO III and IV) than those with early EEC (FIGO I and II) (P = 0.004). To determine the early and advance FIGO stage of EEC, the cutoff value of NK% was calculated as 19.94%. Conclusion: With the decrease of CD4+ T counts, the immune status of patients with EEC is impaired. NK cells may help in the evaluation of the prognosis of patients with EEC and are likely to be an independent risk factor for FIGO staging in patients with EEC. [ABSTRACT FROM AUTHOR]

We aim to investigate the correlation between the expression of estrogen-related receptor γ (ERRγ) and endometrial cancer (EC) progression and to evaluate the potential of ERRγ as a new biomarker for EC diagnosis. We analyzed the ERRγ expression profile and the correlation with the corresponding clinical characteristics of EC samples from The Cancer Genome Atlas (TCGA), the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, and the International Cancer Genome Consortium (ICGC) databases. Immunohistochemical (IHC) analysis was conducted on tissue samples, and enzyme linked immunosorbent assay (ELISA) was used in serum samples to detect the levels of ERRγ. The diagnostic performance of ERRγ proteins was assessed using the receiver operating characteristic (ROC). ERRγ showed notably higher expression in EC tissues than in normal endometrium tissues (P < 0.001), which was consistent with the result of TCGA. Overexpression of ERRγ was significantly associated with deep myometrial invasion of EC (P = 0.004), and fasting blood glucose (FBG) was higher in EC patients with deep myometrial invasion than in those with superficial myometrial invasion (P = 0.040). Further analysis using ELISA showed that the serum ERRγ level was positively correlated with FBG (R = 0.355, P < 0.001). ERRγ is overexpressed in EC and may be involved in regulating glucose metabolism and promoting myometrial invasion of EC. In addition, the area under the ROC curve (AUC) for ERRγ was 0.834, in distinguishing EC patients from healthy individuals, presented 84.0% and 80.0% sensitivity and specificity, respectively, and serum ERRγ has a good diagnostic performance in distinguishing EC patients from healthy people and may be a promising noninvasive biomarker in EC. [ABSTRACT FROM AUTHOR]

Oxygen is critical to energy metabolism, and tumors are often characterized by a hypoxic microenvironment. Owing to the high metabolic energy demand of malignant tumor cells, their survival is promoted by metabolic reprogramming in the hypoxic microenvironment, which can confer tumor cell resistance to pyroptosis. Pyroptosis resistance can inhibit anti-tumor immunity and promote the development of malignant tumors. Hypoxia inducible factor-1α (HIF-1α) is a key regulator of metabolic reprogramming in tumor cells, and estrogen-related receptor α (ERRα) plays a key role in regulating cellular energy metabolism. Therefore, the close interaction between HIF-1α and ERRα influences the metabolic and functional changes in cancer cells. In this review, we summarize the reprogramming of tumor metabolism involving HIF-1α/ERRα. We review our understanding of the role of HIF-1α/ERRα in promoting tumor growth adaptation and pyroptosis resistance, emphasize its key role in energy homeostasis, and explore the regulation of HIF-1α/ERRα in preventing and/or treating endometrial carcinoma patients. This review provides a new perspective for the study of the molecular mechanisms of metabolic changes in tumor progression. [ABSTRACT FROM AUTHOR]

Longan (Dimocarpus longan Lour.) is of great economic significance in South China for its unique taste and nutritional properties. However, longan breeding is mainly based on seedling selection, which generally results in small fruits, low flesh recovery, and few seedless germplasm. Triploid breeding is a central way to improve these problems. In this study, microspore chromosomes were doubled by colchicine and high-temperature treatment to create triploids in longans. The relationship between the development process of male gametophyte of longans and the morphological changes of male flower buds was established. Cytological observation showed that when the male flower buds were in stage I (when the diameter of the flower bud is 1.4–2.0 mm), most of the microspores were at the pachytene to diakinesis stage of meiosis, and the chromosome doubling induction effect was the best at this stage. The results showed that the 2n pollen rate induced by a high temperature of about 38 °C was higher than that induced by colchicine treatment. The highest 2n pollen rate was 5.7% and 5.5% based on the microscopic measurement method and the abnormal separation in tetrad stage estimation method, respectively. Four triploids were successfully obtained from artificial pollination with 2n pollen, with a triploid induction rate of 0.6%. This study will promote ploidy breeding in longan. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the predictive value of the preoperative systemic immune-inflammatory index (SII) for lymph node metastasis (LNM) in endometrial cancer (EC) patients. Methods: We retrospectively included 392 EC patients between January 2013 and January 2019. Data on clinical indicators including age, body mass index (BMI), menopause, serum inflammatory immune index, serum tumor markers, history of diabetes and hypertension, stage, histological type, and myometrial invasion (MI) were collected. The association between clinical indicators and LNM was evaluated. Results: The results indicated that neutrophil (NE), monocyte (MO) counts, SII, cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 199 (CA199), and the expression of estrogen receptor (ER) and Ki67 were higher in EC patients with LNM than in those without LNM (P< 0.05). Lymph vascular space invasion (LVSI) was also associated with LNM (P< 0.05). Consequently, the SII, CA125, CA153 and LVSI were found to be independent risk factors for LNM, and a nomogram including these indicators was performed. The ROC curve analysis showed that compared with a single index, the combination of the SII, CA125, CA153 and LVSI significantly improved the efficiency of diagnosing LNM in EC patients (AUC=0.865, P < 0.001). Moreover, the SII was significantly associated with age, menopause, and FIGO stage (P < 0.05). Further logistic regression analysis suggested that elevated serum SII was an independent risk factor for MI and progression to a higher pathological grade in young premenopausal EC patients. In addition, elevated SII was an independent risk factor for advanced EC progression in age ≥ 55 or postmenopausal EC patients. Conclusion: An elevated SII is an independent risk factor for LNM in patients with EC. In addition, the SII can be used as a predictor of MI and higher pathological grade in young premenopausal EC patients. [ABSTRACT FROM AUTHOR]

Background: China's Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period). Methods: A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost. Results: Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p < 0.001); the rate of colposcopy referral was higher (10.87% versus 6.64%; p < 0.001); and the hazard ratio of CIN2+ diagnosis was 1.64 (95% confidence interval, 1.43–1.88; p < 0.001) after controlling for health insurance status and age. The total costs of the first round of screening (US$66,609 versus US$65,226; p = 0.293) were similar during the two periods. Higher screening coverage (25.95% versus 25.19%; p = 0.007), higher compliance with age recommendations (92.70% versus 91.69%; p = 0.001), lower over-screening (4.92% versus 10.15%; p < 0.001), and reduced unqualified samples (cytology: 1.48% versus 1.73%, p = 0.099; HR-HPV: 0.57% versus 1.34%, p < 0.001) were observed in the HR-HPV genotyping period. Conclusions: Introduction of an HR-HPV genotyping assay in China could detect more CIN2+ lesions at earlier stages and improve programmatic indicators. Evidence suggests that the introduction of HR-HPV genotyping is likely to accelerate the elimination of cervical cancer in China. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the relationship between metabolic syndrome (MetS) and its components and erythrocyte parameters such as red blood cell count (RBC) and hemoglobin (Hb) levels, and their association with the risk of deep myometrial invasion in endometrioid endometrial carcinoma (EEC). Patients and Methods: A total of 473 women diagnosed with EEC between January 2012 and December 2018 were included in the study. MetS was diagnosed using a modified version of the Chinese Diabetes Society 2004 criteria. Demographic and clinical characteristics were stratified by MetS and compared. Logistic regression analyses were performed to calculate the odds ratios (ORs) of myometrial invasion. Results: The prevalence of MetS was 18.8% (89/473). RBC and Hb levels were significantly higher in EEC patients with MetS. RBC and Hb values increased linearly with the number of MetS components. The OR of the MetS risk increased across the RBC quartiles (OR=2.212, 95% confidence interval [Cl]=1.125-4.350, P˂0.05). Among EEC patients with MetS, the OR of deep myometrial invasion increased with the decrease of the RBC quartiles (P=0.037). Similarly, in EEC patients with obesity and hyperglycemia or with ≥ 2 MetS criteria, the lowest RBC level (Q1) was a risk factor for deep myometrial invasion compared with the reference RBC group (Q4, P˂0.05). However, this trend was not evident in EEC patients without MetS and its components. Conclusion: EEC with MetS and its components had higher RBC and Hb levels. The association between the erythrocyte parameters and myometrial invasion differed with MetS. RBC was identified as a risk factor of myometrial invasion in EEC patients with MetS and its components. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about the performance of extended high-risk human papillomavirus (HR-HPV) genotyping triage of cytology showing atypical squamous cells of undetermined significance (ASC-US). This study aims to evaluate the effectiveness of triage with different HR-HPV genotype models among women with ASC-US. Materials and Methods: In this study, all women who underwent cervical cytology and HR-HPV genotyping were enrolled from 2014 to 2017 in China, and those with cytology showing ASC-US were referred for colposcopy and/or biopsy. The endpoint was histological detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). The outcome indicators were the sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs) and colposcopy referral rates. Results: In all, 56,788 women were enrolled in this study, and 2658 (4.97%) women were reported to have ASC-US; 10.1% (242/2393) of women with ASC-US were identified as having CIN2+. The HR-HPV infection rate was 95.0% among all women with ASC-US who were identified as CIN2+, and the top five genotypes with prevalence and risk of CIN2+ were HPV16 (OR=26.38), HPV58 (OR=7.04), HPV18 (OR=4.44), HPV33 (OR=3.38), HPV31 (OR=2.97) and HPV52 (OR=2.96). The HPV16/18/31/33/52/58 model achieved higher sensitivity [91.3 (87.8– 94.9)], specificity [70.0 (68.1– 72.0)], PPV [25.5 (22.4– 28.2)] and NPV [98.6 (97.3– 98.7)] for the triage of ASC-US patients than the other HR-HPV-type combination models, but the colposcopy referral rate (36.2%) was significantly lower than that of the recommended HR-HPV nongenotyping model (47.6%). Conclusion: This study confirms that the specific HR-HPV genotype HPV16/18/31/33/52/58 is an alternative strategy for ASC-US triage and can effectively reduce the high burden of colposcopy referrals in China. [ABSTRACT FROM AUTHOR]

Purpose. This study investigated the infection status and relationship between other common lower genital tract infectious pathogens and high-risk human papillomavirus (HR-HPV) in the high-grade cervical lesions. Methods. Overall, 882 patients were enrolled in this retrospective study, of which 339 patients (≥HSIL group) were confirmed with high-grade squamous intraepithelial lesions (HSIL) or cervical squamous cell carcinoma (SCC), while 543 patients (≤LSIL group) were diagnosed with low-grade squamous intraepithelial lesions (LSIL) or normal cervical pathology diagnosis. Cervical swab specimens were tested for HPV, pathogenic bacteria (PB), U. urealyticum (UU), M. hominis (MH), and C. trachomatis (CT) in both groups. Results. The infection rates of HR-HPV, PB, UU (at high density), and CT were higher in the ≥HSIL group than in the ≤LSIL group (P < 0.001); however, higher infection rates with MH were not observed (P > 0.05). PB, UU, and CT were associated with HR-HPV infection (P < 0.001). The PB and UU infection rates in the ≥HSIL group were significantly different from those in the ≤LSIL group, regardless of whether there was an HR-HPV infection at the same time (P < 0.05). However, this was not the case for the CT (P > 0.05). Furthermore, 259 pathogenic bacterial strains were detected in 882 cases. The difference in the distribution of pathogenic bacterial flora in the different grades of cervical lesions had no statistical significance, which was prioritized over Escherichia coli (P > 0.05). Conclusion. PB, UU, and CT infection is associated with susceptibility to HR-HPV, HR-HPV coinfection with these pathogens might increase the risk of high-grade cervical lesions, and PB and UU might be independent risk factors for cervical lesions. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the inflammatory-immune cells in the peripheral blood of women with polycystic ovary syndrome (PCOS) and assessed the potential correlation between inflammatory-immune cells and infertility in PCOS women. Materials and Methods: In this case–control study, the profiles of lymphocyte subsets were analyzed by flow cytometry. White blood cells (WBC), neutrophils (Neu), lymphocytes, Ferriman–Gallwey (F–G) score, testosterone, prolactin, follicle-stimulating hormone, luteinizing hormone, fasting blood glucose, and fasting plasma insulin were measured, together with body mass index. Association between inflammatory-immune cells and PCOS was evaluated. Moreover, inflammatory-immune cells of the PCOS women with infertility were evaluated, and the relative operating characteristic (ROC) curve and cutoff values were calculated. Results: The number of WBC, Neu, and lymphocytes was higher in PCOS women than controls (P< 0.05). The percentages of total T lymphocytes, CD4+T, and NK were significantly increased in the PCOS group (P< 0.001). The CD4/CD8 ratio was obviously elevated for increasing CD4+T (P< 0.05). Consequently, T%, CD4+T%, and NK% were found to be the independent risk factors of PCOS by ROC curve and multivariate logistic regression analysis. Furthermore, only NK% was significantly higher in PCOS women with infertility than those who had PCOS without infertility (P< 0.001). To diagnose infertility in PCOS, the cutoff value of NK% was calculated as 16.43%. Conclusion: These findings suggest that the pathogenesis of PCOS is related to immune cells including T, CD4+T, and NK cells. NK cells are likely to be a potential predictive factor for PCOS women with infertility. [ABSTRACT FROM AUTHOR]

Using a large proprietary database of intraday high‐frequency trading, we investigate the trading strategies of institutional investors in dealing with the negative environmental event disclosure of listed companies and their impact on markets, aiming to reveal the mechanism of the lack of "green efficiency" in China's capital market from the perspective of institutional investors. The results show that institutional investors react to negative environmental events prior to the announcements, indicating premature information leakage in the market; in addition, their trading behaviors mitigate the immediate effect of negative environmental event announcements on stock price. After the event is disclosed, institutional investors engage in short‐term selling and long‐term buy and hold. This trading strategy undermines the irrational selling of individual investors in the event of disclosure, short‐term decline in stock price, and long‐term reversal of market overreaction. In a China context, institutional investors generally take environmental information into consideration. However, they fail to recognize the long‐term value effect of negative environmental events and instead cater to trading strategies towards market volatility. [ABSTRACT FROM AUTHOR]

HColonDB (Human Colon cancer Database) is an important database which integrates genes, pathways, networks, drugs, and other information related to colon cancer. The purpose of the database is to provide a platform for the systematic research of colon cancer. The relationships between genes and pathways, genes and networks, and networks and pathways are obtained from the database KEGG. Furthermore, the information of the drugs used to treat colon cancer is available in HColonDB, which is collected and organized from DrugBank and PubChem database. In brief, we have summarized 81 genes, 112 pathways, 108 networks, and 15 drugs associated with colon cancer. The current version of HColonDB contains 322 associations between genes and pathways, 242 associations between genes and networks, and 68 associations between networks and pathways. In addition, HColonDB provides a friendly interface for users to browse and search. We hope that the database can make it more convenient for researchers to get the data they need and help in the treatment of colon cancer. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the high-risk human papillomavirus (HR-HPV) prevalence in a hospital-based population using the Cervista® and to determine the clinical value and significance of Cervista for cervical cancer screening in Fujian Province, China.Patients and Methods: In a hospital-based population, a total of 10,771 women from the Fujian Province were screened for cervical cancer and precancerous lesions using the thinprep cytologic test (TCT) and/or the Cervista. Women with HR-HPV infection and/or abnormal TCT were referred for colposcopy and biopsy. Pathological diagnosis was used as the gold standard.Results: The overall HR-HPV prevalence was 16.57%. Among 10,229 cases, 976 had abnormal cytology results, of which, the HR-HPV positivity rate was 60.35% in this opportunistic screening population. The most common HR-HPV infection style was a simple infection. The most common species was A9 which was also the most prevalent species in all age. The women with CIN2+ (high-grade squamous intraepithelial lesion [HSIL]), especially cancer, were mostly concentrated in the age from 51 to 60 years old. The peak of CIN1 (low-grade squamous intraepithelial lesion, LSIL) prevalence was in the women aged 31-40. When using CIN1+, CIN2+ and CIN3+ as observed endpoints, the sensitivities were 86.07%, 92.73%, and 93.30% and negative likelihood ratio (NPV) were 99.15%, 99.75% and 99.83%, respectively. Cervista and TCT co-testing achieved the highest sensitivity and the lowest NLR.Conclusion: The Cervista could be easily introduced in clinical practice in combination with TCT for cervical cancer screening in China. Patients with species A9 infection require a more actively clinical intervention. [ABSTRACT FROM AUTHOR]

Purpose: Currently, the associations between type-specific high-risk human papillomavirus (HR-HPV) viral loads and cervical lesions are still inconsistent. We aimed to assess the type-specific HR-HPV viral load as a risk triage indicator for development of high-grade squamous intraepithelial lesion or worse (≥HSIL).Patients and methods: A total of 19,446 women who underwent primary screening for cervical cancer using Cervista® HR-HPV and cytology assays were enrolled. The viral loads of 1,396 HR-HPV-positive specimens confirmed by Cervista® assay were detected by BioPerfectus Multiplex Real-Time PCR assay. The correlation between viral loads and cervical lesions was analyzed. The optimal cutoffs of individual HR-HPV viral loads used to predict ≥HSIL were determined from the receiver operating characteristic curve. A logistic regression model was used to analyze the relationship between covariates and the probability of ≥HSIL.Results: The viral loads of HPV-16, -31, -33, -52, and -58 were positively correlated with the severity of the cervical lesion, which was significantly elevated in patients with ≥HSIL, whereas those of HPV-18, -45, -56, -59, and other types were not. The optimal cutoffs of the log10-transformed viral loads for HPV-16, -31, -33, -52, and -58 in identifying ≥HSIL were 4.26, 4.46, 4.48, 4.36, and 4.26 copies per 10,000 cells, respectively. Furthermore, multivariate analysis indicated that type-specific viral loads of HPV-16, -31, -33, -52, and -58 exceeding the cutoffs could be independent risk factors for the incidence of ≥HSIL.Conclusion: The BioPerfectus Multiplex Real-Time PCR viral load assay provides viable triage for ≥HSIL when using appropriate cutoff levels. [ABSTRACT FROM AUTHOR]

Purpose: To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms.Methods: The mRNA and protein expression levels of ERRα and estrogen receptor α (ERα) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERRα-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERRα (siRNA-ERRα), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry. After treatment with siRNA-ERRα, the expression profiles of transcription factors (TFs) were analyzed by protein/DNA arrays in EC cells.Results: The relative mRNA levels of ERRa in RL-952 (1±0.0831) and AN3-CA (1.162±0.0325) were significantly higher than those in HEC-1A (0.3081±0.0339) and HEC-1B (0.1119±0.0091) (P [ABSTRACT FROM AUTHOR]

As a notable feature of malignant tumors, invasion and metastasis are important events in the process of tumor progression. Amiloride, a synthetic inhibitor of urokinase plasminogen activator (uPA), is involved in these events. To evaluate the therapeutic value of amiloride in cervical cancer, HeLa cells were used as in vitro cellular models. The migration and invasion abilities of HeLa cells, in addition to the mRNA expression of matriptase, uPA, uPA receptor and 72 kDa type IV collagenase (MMP‑2), were detected using scratch assays, Transwell chamber assays and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The results of RT‑qPCR demonstrated that the mRNA expression of uPA and MMP‑2 in HeLa cells was downregulated significantly in a dose‑dependent manner when incubated with various concentrations of amiloride for 24 h. The migration distance of HeLa cells was significantly shorter at 6, 12 and 24 h following incubation with amiloride (P<0.01), and there was a positive correlation between cell migratory ability and cellular uPA protein expression level (r=0.955, P<0.01). The number of HeLa cells that penetrated the Matrigel following incubation for 24 h with different concentrations of amiloride decreased significantly compared with the control group, indicating that cell invasiveness was positively correlated with the protein expression level of uPA in the cells (r=0.993, P<0.01). The present study demonstrated that amiloride was able to specifically inhibit the mRNA expression levels of uPA in HeLa cells, and sequentially downregulate the mRNA expression of downstream MMP‑2 in the uPA system, thereby suppressing the migratory and invasive ability of HeLa cells. Therefore, amiloride may be a promising therapeutic target for the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: New screening techniques may affect the optimal approaches for the prevention of cervical cancer. We evaluated the cost-effectiveness and accuracy of alternative screening strategies to provide evidence for cervical cancer screening guidelines in China. Methods: In total, 32,306 women were enrolled. The current screening with Cervista® high-risk human papillomavirus (HR-HPV) nongenotyping and cytology cotesting (Cervista® cotesting) was compared with PCR-reverse dot blot HR-HPV genotyping and cytology cotesting (PCR-RDB cotesting). All eligible participants were divided into Arm 1, in which both HR-HPV assays were performed, and Arms 2 and 3, in which the PCR-RDB HPV or Cervista® HR-HPV assay, respectively, was performed. Outcome indicators included the cases, sensitivity, negative predictive value (NPV), colposcopy referral rate and cost of identifying cervical intraepithelial neoplasia of grade 2/3 or worse (CIN2+/CIN3+). Results: Among the eligible participants, 18.4% were PCR-RDB HR-HPV-positive, while 16.9% were Cervista® HR-HPV-positive, which reflects good agreement (k = 0.73). PCR-RDB cotesting identified more CIN3+ cases than Cervista® cotesting in the first round of screening in Arm 1 (37 vs 32) and Arms 2/3 (252 vs 165). The sensitivity and NPV of PCR-RDB cotesting for identifying CIN3+ in Arm 1 (sensitivity: 94.9% vs 86.5%; NPV: 99.9% vs 99.7%) and Arms 2/3 (sensitivity: 95.1% vs 80.9%; NPV: 99.9% vs 99.6%) were higher than those of Cervista® cotesting, but the cost was similar. Conclusions: The PCR-RDB HR-HPV genotyping and Cervista® HR-HPV assay results were consistent. PCR-RDB cotesting possesses optimal cost-effectiveness for cervical cancer screening in China, which has the highest number of cases globally but low screening coverage. [ABSTRACT FROM AUTHOR]

ICE1 (inducer of CBF expression 1) encodes a typical MYC-like basic helix-loop- helix (bHLH) transcription factor that acts as a pivotal component in the cold signalling pathway. In this study, DlICE1 , a novel ICE1-like gene, was isolated from the southern subtropical fruit tree longan (Dimocarpus longan Lour.). DlICE1 encodes a nuclear protein with a highly conserved bHLH domain. DlICE1 expression was slightly upregulated under cold stress. Overexpression of DlICE1 in Arabidopsis conferred enhanced cold tolerance via increased proline content, decreased ion leakage, and reduced malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation. Expression of the ICE1-CBF cold signalling pathway genes, including AtCBF1/2/3 and cold-responsive genes (AtRD29A, AtCOR15A, AtCOR47 and AtKIN1), was also significantly higher in DlICE1 -overexpressing lines than in wild-type (WT) plants under cold stress. In conclusion, these findings indicate that DlICE1 is a member of the bHLH gene family and positively regulates cold tolerance in D. longan. • DlICE1 is a novel longan MYC-type ICE1-like transcription factor. • DlICE1 expression of longan leaves was upregulated under cold stress. • DlICE1 overexpression in Arabidopsis enhanced cold tolerance by regulating physiological parameters and cold response genes. [ABSTRACT FROM AUTHOR]

For ocean pollution emergencies, decision-makers need to quickly know the location of the pollutant for quick assessment and response strategies. In this study, an integrated operational forecasting model coupling a non-Fickian particle-tracking diffusion model based on fractional Brownian motion and geographic information system (GIS) has been developed to implement an operating system for pollutant drift forecasting. The software was developed in C# and C++ language using ArcGIS Engine functions which provides improved visualization and user-friendly and automatic tools for simulation in a geographically referenced environment. The capabilities and effectiveness of the developed software were illustrated by predicting red tide drift through calibration with field observations. This visualized operational forecasting software provides a quick and easy deployable tool for decision-makers in quick response to emergency ocean pollution events. [ABSTRACT FROM AUTHOR]

The Yangtze River Estuary (YRE) is vulnerable to the accelerated sea level rise (SLR). In this study, a three-dimensional hydrodynamic and salinity transport model, with a high resolution unstructured mesh and spatially varying bottom roughness, is applied to quantify the influences of SLR on saline water intrusion in the YRE. The model has well been validated through observation data of tidal level, flow velocity and direction, and salinity. The performances of four scenarios of the present sea level (PSL) as well as 0.5, 1 and 2 m SLR reveal that (1) the isohaline shifts upstream nonlinearly in the YRE with SLR, and non-uniform in the spatial distribution under the same SLR. The isohalines of 1, 2 and 5 psu near the north bank of the South Branch intrude farther upstream than those near the south bank, and the upstream advance distance of 0.45 psu isohaline is much longer than those of 1, 2 and 5 psu isohalines under the same SLR. (2) The spillover of saline water from the North Branch into the South Branch intensifies with SLR, while the salinity in the lower reach of the North Branch is reduced due to increased low salinity flow from the South Branch and the North Channel caused by SLR. (3) The durations of undrinkable water increase at four reservoirs with SLR, and four reservoirs cannot intake raw drinking-water in the dry season in the 2 m SLR scenario. (4) A regression analysis obtains a quantitative quadratic expression between salinity and SLR. Finally, the effects of the operation of the Three Gorges Reservoir and more SLR scenarios on the salinity, and two different approaches for SLR simulations are also discussed. [ABSTRACT FROM AUTHOR]