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Introduction Listeria monocytogenes (LM) is an important food-borne pathogen, and the risk of its ingestion is a serious public health issue. The better its environmental adaptation mechanisms and pathogenicity are understood, the better the risk it poses can be countered. The regulatory role of the small non-coding RNA (sRNA) rli106 in the environmental adaptation and pathogenicity of LM is still unclear and this study investigated that role through its biological function. Material and Methods An LM-Δrli106 gene deletion strain and an LM-Δrli106/rli106 gene complementation strain were constructed using the homologous recombination technique. Then, the adaptation of these strains to temperature, alkalinity, acidity, salinity, ethanol and oxidative stressors, their biofilm-forming ability and their pathogenicity in mice were investigated to show the regulatory roles of sRNA rli106 in LM. The target gene of rli106 was also predicted, and the interaction between it and rli106 was verified by a two-plasmid co-expressing system based on E.coli and Western blot analysis. Results The adaptation of LM-Δrli106 to environmental stressors of pH 9, 5% NaCl and 8% NaCl, 3.8% ethanol and 5 mM H2O2 was significantly reduced when compared to the parental (LM EGD-e) and complementation strains. Also, the biofilm formation, cell adhesion, invasion, intracellular proliferation and pathogenicity of LM-Δrli106 in mice were significantly reduced. The results of two-plasmid co-expression and Western blot showed that rli106 can interact with the mRNA of the predicted DegU target gene. Conclusion The sRNA rli106 may positively regulate the expression of the DegU gene in LM. This study sheds light on its regulatory roles in environmental adaptation and pathogenicity, providing new insights into the molecular mechanism of sRNA mediation in LM .

Introduction Nematodes of the Trichuris genus are commonly reported parasites that can cause trichuriasis in many animals, which leads to inflammation, intestinal bleeding and reductions of productivity in livestock. Knowledge of the prevalence of Trichuris infestation in the Tianshan ovine population and of the nematode species parasitising the population is not exhaustive, and this study aimed to expand the knowledge. Material and Methods A total of 1,216 sheep slaughtered in five pasture areas in the Tianshan Mountains of Xinjiang were investigated and a phylogenetic analysis based on the mitochondrial cox1 gene was performed to clarify the genetic relationships of the various Trichuris species. Results Sheep totalling 1,047 were infected with Trichuris spp. establishing the rate at 86.1%. Using a morphological protocol, six documented and one undefined species were identified, namely T. gazellae, T. lani, T. ovina, T. longispiculus, T. concolor, T. discolor and Trichuris sp. Among them, T. gazellae and T. lani were the dominant species, accounting for 34.5% and 31.0% of Trichuris spp., respectively. Phylogenetic analysis divided the detected species of Trichuris spp. into two genetic clades (clade I and clade II). The six documented species that can infect sheep and the undefined species were clustered into clade I, with inter- and intra-species genetic diversity apparent. Conclusion This survey described in detail the morphological characteristics of six known and one undefined species of Trichuris, which not only enriched the taxonomic information on record regarding Trichuris spp., but also provided valuable epidemiological data for the prevention and control of trichuriasis in sheep.

1. Basic characteristics of endometrial hyperplasia and EC patients. Supplementary Table 2. Basic information of clinical samples for Immunohistochemistry. Supplementary Table 3. Primers used.

Supplementary Materials and Methods and Supplementay Figure legends

Persistent unopposed estrogen stimulation is a central oncogenic mechanism driving the formation of type I endometrial cancer. Recent epidemiologic and clinical studies of endometrial cancer have also revealed a role for insulin resistance, clinically manifested by chronic inflammation. However, the role of inflammation in estrogen-driven endometrial cancer is not well characterized. In this study, we investigated the association between infiltrating macrophages and estrogen sensitivity in endometrial cancer. Evaluating tissue samples and serum from patients with precancerous lesions or endometrial cancer, we found that tissue macrophage infiltration, but not serum estradiol levels, correlated positively with endometrial cancer development. Furthermore, IL4/IL13-induced CD68+CD163+ macrophages enhanced the proliferative effects of estradiol in endometrial cancer cells by upregulating estrogen receptor alpha (ERα), but not ERβ. Mechanistic investigations revealed that CD68+CD163+ macrophages secreted cytokines, such as IL17A, that upregulated ERα expression through TET1-mediated epigenetic modulation of the ERα gene. Overall, our findings show how cytokines produced by infiltrating macrophages in the endometrial microenvironment can induce epigenetic upregulation of ERα expression, which in turn sensitizes endometrial cells to estrogen stimulation. The concept that inflammation-induced estrogen sensitivity in the endometrium acts as a driver of type I endometrial cancer has implications for infiltrating macrophages as a prognostic biomarker of progression in this disease setting. Cancer Res; 76(6); 1354–66. ©2016 AACR.

IL-17A or overexpression of ERα promoted estradiol-driven endometrial cancer cell proliferation

Induction of CD68+CD163+ macrophages from THP-1 cells

IL-17 receptor antibody compromises the effect of IL-17A on ERα transcription up-regulation

Serum estradiol levels were not elevated in patients with endometrioid adenocarcinoma after stratification by pathologic grading

Semi-quantitative evaluation of the immunohistochemical staining of IL-17A, TET1, 5-hmC, and ERα expression in endometrial hyperplasia and cancer lesions

The expression pattern of ERα in different cell lines

Salmonella Typhimurium (STM) is one of the most important food-borne bacteria that seriously harm livestock and human beings, which is capable of regulating the expression of its own genes in a variety of ways to adapt to a wide variety of adverse environmental stresses. To understand the regulatory roles of sRNA STnc1480 on the capability of STM, the STnc1480 gene-deficient strain △STnc1480 and its complement strain △STnc1480/STnc1480 were generated, and the impacts of STnc1480 gene deficiency on the capability of responding to different environmental stresses, BF formation and pathogenicity were analyzed, respectively. Then, the target genes that were regulated by STnc1480 were also analyzed and explored. Compared with parent and complement strains, the deficiency of the STnc1480 gene significantly reduced the BF formation. Moreover, the capacities of adhesion and invasiveness of the △STnc1480 strain to macrophages were also significantly reduced, while the LD50 in mice was significantly increased. The bacterial loads in liver and spleen were significantly reduced, and the pathological damage was alleviated. It was confirmed that the STnc1480 could be complementary to the 5’-UTR (-52 to -71 bases) region of lpfA mRNA. The bacterial dual plasmid reporting system confirmed that STnc1480 was capable of interacting with the mRNA of the lpfA gene, suggesting that STnc1480 can regulate the 5’-UTR of the lpfA mRNA at post transcription level to reduce the expression of the bacterial fimbria, thus reducing the BF formation and pathogenicity of STM.

To investigate the feasibility of volumetric apparent diffusion coefficient (ADC) histogram analysis for prediction of fertility-sparing treatment (FST) response in patients with endometrial cancer (EC).Pretreatment data of 54 EC patients with FST were retrospectively analyzed. Treatment response at each follow-up was pathologically evaluated. The associations of ADC histogram metrics (volume, minADC, maxADC, meanADC; 10th, 25th, 50th, 75th and 90th ADC percentiles; skewness; kurtosis) and baseline clinical characteristics with complete response (CR) at the second and third follow-ups, two-consecutive CR, and recurrence at the final follow-up were evaluated by uni- and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used for diagnostic performance evaluation.Compared with non-CR patients, CR patients had significantly higher minADC and 10th and 25th ADC percentiles at the second follow-up (P = 0.008, 0.039, and 0.034, respectively) and higher minADC, older age, lower HE4 level, and higher overweight rate at the third follow-up (P = 0.001, 0.040, 0.021, and 0.004, respectively). Patients with two-consecutive CR had a significantly higher minADC than those without (P = 0.018). There was no association between ADC metrics or clinical characteristics and recurrence (all P0.05). MinADC yielded the largest AUC in predicting CR (0.688 and 0.735 at the second and third follow-up, respectively) and the presence of two-consecutive CR (0.753). When combined with patient age and HE4 level, the prediction of CR could be further improved at the third follow-up, with an AUC of 0.786.Pretreatment minADC could be a potential imaging biomarker for predicting FST response. Clinical characteristics may have incremental value to minADC in predicting CR.

Fascioliasis is an important zoonotic helminthic disease caused by Fasciola hepatica and poses a serious threat to global public health. To evade the immune response of its host (humans or animals), F. hepatica secretes various antioxidant enzymes such as glutathione transferase (GST) to facilitate its invasion, migration and parasitism in vivo. To investigate the biological functions of a novel omega-class GST (GSTO), the molecular features of GSTO2 of F. hepatica were analyzed by online software, and the biochemical properties in vitro of recombinant GSTO2 (rGSTO2) were dissected. Then, the regulatory roles of rGSTO2 protein in murine macrophages in vitro were further explored. The results revealed that the GSTO2 gene encodes 254 amino acids, which harbor the characteristic N-terminal domain (βαβαββα) and C-terminal domain (α-helical) of the cytoplasmic GST superfamily. GSTO2 was mainly expressed in F. hepatica vitelline follicles, intestinal tract, excretory pores and vitelline cells, with thioltransferase and dehydroascorbate reductase activities. Moreover, rGSTO2 protein could be taken up by murine macrophages and significantly inhibit the viability of macrophages. In addition, rGSTO2 protein could significantly promote apoptosis and modulate the expression of cytokines in macrophages. These findings suggested that F. hepatica GSTO2 plays an important role in modulating the physiological functions of macrophages, whereby this protein might be involved in immunomodulatory and anti-inflammatory roles during infection. This study provided new insights into the immune-evasion mechanism of F. hepatica and may contribute to the development of a potential anti-inflammatory agent.Caractérisation moléculaire d’une nouvelle GSTO2 de Fasciola hepatica et ses rôles dans la modulation des macrophages murins.La fasciolase est une importante maladie helminthique zoonotique causée par Fasciola hepatica, qui constitue une menace sérieuse pour la santé publique mondiale. Pour échapper à la réponse immunitaire de son hôte (humain ou animal), F. hepatica sécrète diverses enzymes antioxydantes telles que la glutathion transférase (GST) pour faciliter son invasion, sa migration et son parasitisme in vivo. Pour étudier les fonctions biologiques d’une nouvelle GST de classe oméga (GSTO), les caractéristiques moléculaires de la GSTO2 de F. hepatica ont été analysées par un logiciel en ligne et les propriétés biochimiques in vitro de sa protéine recombinante (rGSTO2) ont été disséquées. Ensuite, les rôles régulateurs de la protéine rGSTO2 sur les macrophages murins in vitro ont été explorés plus avant. Les résultats ont révélé que le gène GSTO2 code pour 254 acides aminés, qui abritent le domaine N-terminal caractéristique (βαβαββα) et le domaine C-terminal (α-hélicoïdal) de la superfamille GST cytoplasmique. Chez F. hepatica, GSTO2 était principalement exprimée dans les follicules vitellins, le tractus intestinal, les pores excréteurs et les cellules vitellines, avec des activités de thioltransférase et de déhydroascorbate réductase. De plus, la protéine rGSTO2 a pu être absorbée par les macrophages murins et inhiber de manière significative la viabilité des macrophages. Enfin, la protéine rGSTO2 a pu favoriser de manière significative l’apoptose et moduler l’expression des cytokines dans les macrophages. Ces résultats suggèrent que la GSTO2 de F. hepatica joue un rôle important dans la modulation des fonctions physiologiques des macrophages, cette protéine pouvant être impliquée dans des rôles immunomodulateurs et anti-inflammatoires au cours de l’infection. Cette étude a fourni de nouvelles informations sur le mécanisme d’évasion immunitaire de F. hepatica et pourrait contribuer au développement d’un agent anti-inflammatoire potentiel.

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

Objective This study aimed to evaluate the efficacy of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young patients with endometrial atypical hyperplasia (EAH) and early stage endometrial cancer (EEC) who wished to preserve their fertility. Methods Patients with EAH (n = 120) or well-differentiated EEC (n = 40, FIGO stage IA, without myometrial invasion) were retrospectively included. All patients received constant oral progestin combined with hysteroscopic evaluation every 3 months until achieving complete response (CR). The location, number and size of each suspected lesion or cluster were detailly recorded during the hysteroscopy. Results The median age was 32.0 year-old (range, 22–47 year-old). Totally 148 patients (97.4%) achieved CR while 3 EAH and 1 EEC patients presented with disease progression, and 8 patients were still in treatment. The mean treatment duration for achieving CR was 6.7 ± 0.3 months (range, 1–18 months). After adjusting for patient age, body mass index (BMI), history of pregnancy and type of conservative therapies, lesion size ≤2 cm (OR, 0.701; 95% CI, 0.496–0.991; P = 0.045) was significantly correlated with shorter treatment time to achieve CR. Among 60 patients attempted to conceive after achieving CR, 45.0% (15/60) had been pregnant, 25.0% (15/60) delivered live birth, 13.3% (8/60) are still in pregnancy, while 6.7% experienced spontaneous abortion. Conclusion Comprehensive hysteroscopic evaluation and lesion resection plus progestin therapy seem to be an effective and safe fertility sparing therapy for patients with EAH or EEC. Endometrial lesion size ≤2 cm correlated with a shorter treatment period to achieve CR.

Continuous estrogen signaling is thought to be the main mechanism causing endometrial cancer (EC). Studies have demonstrated that CD163+ macrophages could promote the development of estrogen-dependent EC, but the mechanisms involved remain unclear. We found that CD163+ macrophages were the dominant macrophages in atypical endometrial hyperplasia and cancer, and their infiltration was positively associated with ERα expression. CD163+ macrophages mainly increased ERα protein levels but with little upregulatory effect on ESR1 (ERα coding gene) transcripts. The ubiquitin-editing enzyme A20, screened from the endometrial microarray obtained from mice receiving a high-fat diet and sustained estrogen-intervened, was highly expressed in endometrial lesions rich with CD163+ macrophages, and positively correlated with ERα expression. Similarly, A20 and ERα were both upregulated by CD163+ macrophages via cytokines such as IL1α, IL17A and TNFα. Mechanistically, A20 overexpression in EC cells prolonged ERα protein half-life without affecting ESR1 transcripts. A20 increased functional ERα protein levels and enhanced estrogen-driven EC cell proliferation through preventing ERα protein degradation by its deubiquitinase activity. Our study revealed that A20-mediated deubiquitination of ERα might be an important mechanism by which CD163+ macrophages sensitize EC cells to estrogen.

Small RNAs (sRNAs) are essential virulent regulators in Salmonella typhimurium (STM). To explore the role of sRNA STnc150 in regulating STM virulence, we constructed a STnc150 deletion strain (ΔSTnc150) and its complementary strain (ΔSTnc150/C). Then, we compared their characteristics to their original parent strain experimentally, identified the target genes of STnc150 and determined the expression levels of target genes. The results showed that the ΔSTnc150 strain exhibited delayed biofilm formation, enhanced adhesion to macrophages, significantly reduced LD50, increased liver and spleen viral loads and more vital pathological damaging ability than its parent and complementary strains. Further, bioinformatics combined with the bacterial dual plasmid reporter system confirmed that the bases 72–88 of STnc150 locating at the secondary stem-loop structure of the STnc150 are complementary with the bases 1–19 in the 5′-terminal of fimA mRNA of the type 1 fimbriae subunit. Western blot analysis showed that fimA protein level was increased in STnc150 strain compared with its parent and complementary strains. Together, this study suggested that STnc150 can down-regulate STM fimA expression at the translation level, which provided insights into the regulatory mechanisms of sRNAs in virulence of STM.

Background Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Objective This study aimed to investigate the incidence of ovarian malignant involvement in young and premenopausal endometrioid endometrial cancer and study the possible risk factors. Methods Premenopausal patients 45 years of age or younger with endometrioid endometrial cancer treated at the OB/GYN Hospital of Fudan University between 2009 and 2013 were identified. The incidence of ovarian malignant involvement in young and premenopausal endometrioid endometrial cancer patients were calculated and the possible risk factors were investigated. Results A total of 144 younger (age ≤ 45, premenopausal) patients with endometrioid endometrial cancer were identified and coexisting malignant ovarian neoplasms were detected in 6 patients. Univariate analysis revealed that deeper myometrial invasion, positive lymphonode metastasis, positive LVSI, and high histologic grade (G2-G3) were associated with ovarian involvement in younger endometrial cancer patients. However, multivariate analysis revealed that only deep myometrial invasion was an independent risk factors for ovarian involvement (OR = 12.81, P = 0.046). Conclusion In conclusions, the incidence of coexisting ovarian malignant neoplasms in young and premenopausal patients with endometrioid endometrial cancer is low, and these findings may facilitate preoperative counseling of patients and decision making at the time of surgery.

Large amount of clinical evidence has demonstrated that insulin resistance is closely related to oncogenesis of endometrial cancer (EC). Despite recent studies showed the up-regulatory role of insulin in G protein-coupled estrogen receptor (GPER/GPR30) expression, GPER expression was not decreased compared to control when insulin receptor was blocked even in insulin treatment. The purpose of this study was to explore the possible mechanism by which insulin up-regulates GPER that drives EC cell proliferation. For this purpose, we first investigated the GPER expression in tissues of endometrial lesions, further explored the effect of GPER on EC cell proliferation in insulin resistance context. Then we analyzed the role of Ten-Eleven Translocation 1 (TET1) in insulin-induced GEPR expression and EC cell proliferation. The results showed that GPER was highly expressed in endometrial atypical hyperplasia and EC tissues. Mechanistically, insulin up-regulated TET1 expression and the latter played an important role in up-regulating GPER expression and activating PI3K/AKT signaling pathway. TET1 mediated GPER up-regulation was another mechanism that insulin promotes EC cell proliferation.

Background: Insulin resistance (IR) has been well studied in the initiation and development of endometrial endometrioid carcinoma (EEC). As yet, it has been largely neglected for estrogen sensitivity in local endometrium in hyperinsulinemia-induced systemic microenvironment. The aim of this study was to investigate the role of insulin in regulating estrogen sensitivity and explore the potential mechanisms in insulin-driven inflammatory microenvironment. Methods: We first investigated the effect of insulin on estradiol-driven endometrial cancer cells proliferation in vitro to address the roles of insulin in modulating estrogen sensitivity. Then GPER, ERα and TET1 in EEC samples with or without insulin resistance were screened by immunohistochemistry to confirm whether insulin resistance regulates estrogen receptors. Further mechanism analysis was carried out to address whether TET1 was mediated epigenetic modulation of GPER in insulin-induced microenvironment. Results: Insulin enhanced estradiol-driven endometrial cancer cells proliferation by up-regulating G-protein-coupled estrogen receptor (GPER) expression, but not ERα or ERβ. Immunohistochemistry of EEC tissues showed that GPER expression was greatly increased in endometrial tissues from EEC subjects with insulin resistance and was positively correlated with Ten-eleven-translocation 1 (TET1) expression. Mechanistically, insulin up-regulates TET1 expression, and the latter, an important DNA hydroxymethylase, could up-regulate GPER expression through epigenetic modulation. Conclusion: This study identified TET1 as the upstream regulator of GPER expression and provides a possible mechanism that insulin-induced positive regulation of estrogen sensitivity in endometrial cancer cells. Increasing expression of GPER through TET1-mediated epigenetic modulation may emerge as the main regulator to enhance the response of endometrial cancer to estrogen in insulin-driven inflammatory microenvironment.

Objectives The present study aimed to evaluate the clinicopathologic features, prognosis and follow-up of uterine smooth muscle tumor of uncertain malignant potential (uSTUMP) in a single institution. In addition, we described the obstetric outcomes after uterine-preserving surgery for uSTUMP. Methods A retrospective chart review was performed of patients diagnosed with uSTUMP between January 2001 and December 2015 in the Obstetrics and Gynecology Hospital, Fudan University. Variables of interest included the patients’ demographics, morphological parameters, therapeutic results, time to recurrence, disease-free and overall survival, and subsequent obstetric outcomes. Pathology reviews were carried out by two pathologists (Z.L.H. and Z.C.Y.). Results Nineteen patients with an initial diagnosis of uSTUMP were included in the study, and three of them were interpreted as sarcoma after slide review. In total, 16 patients with a final diagnosis of STUMP were available. The recurrence-free survival (RFS) curves differed significantly between uSTUMP and sarcoma group (p=0.003). One uSTUMP patient (6.3%) developed a recurrence as uSTUMP during the follow-up period. The clinical characteristics and histology features did not show significant correlations with recurrence, nor was the surgery type (uterus conserving versus hysterectomy) and surgery approach. Six uSTUMP patients requested uterine-preserving treatment, and two of whom wanted to become pregnant. Both of them (2/2) successfully delivered live birth without tumor recurrence. Conclusions The patients of uSTUMP deserve a pathology review process in centers with experience. Recurrences can be rapid or slow in the form of uSTUMP or LMS. Fertility-preserve management is worth attempting in young patients with close follow-up.

Endometrial cancer (EC) has recently become a major gynecological cancer and endometrial hyperplasia increases the risk for developing EC. Previous studies have reported that human high temperature requirement factor A3 (HtrA3), a member of ATP independent serine proteases family, is involved in endometrial carcinogenesis. However, the underlying mechanism of HtrA3 function is unclear in endometrial hyperplasia and cancer. In this study, we investigated that HtrA3 expression was reduced in endometrial hyperplasia as well as EC. The circulating levels of HtrA3 were also significantly reduced in both atypical hyperplasia and EC. Whether hypoxia is involved in the reduction of HtrA3 in EC was further investigated. Immunohistochemistry (IHC) scores of Glut1 and HtrA3 in type 1 and type 2 EC tissues showed the inverse correlation. And hypoxic condition reduced the expression of HtrA3. Furthermore, silencing HtrA3 promoted EC cell migration. Our study demonstrated the reduced levels of HtrA3 in endometrial hyperplasia including atypical hyperplasia which is a premalignant condition; and as the degree of hypoxia increases in EC, HtrA3 eventually loses its expression. Hypoxia is responsible for the reduction of HtrA3 which in turn promotes EC progression. These findings suggested that HtrA3 is an important adaptor in hypoxic regions that drives endometrial cancer development.

Continuous estrogen signaling is thought to be the main mechanism causing endometrial cancer (EC). Studies have demonstrated that CD163

Perivascular epithelioid cell tumor (PEComa) is a rare condition and the recognition of this condition is limited. Here we report five cases of uterine PEComa to add to the limited understanding of this rare condition. Five cases from Obstetrics and Gynecology Hospital of Fudan University were diagnosed as uterine PEComas. We collected the patients’ clinical and pathological data as well as their outcomes. All the five cases were diagnosed post-operationally. Fertility-sparing surgery was done for the first case and had a mass resection only. She delivered a healthy boy through the cesarean section in November 2016 and neither recurrence nor metastasis was found for 71 months. Hysterectomy was done for the other four cases. Adjuvant chemotherapy was also given for case 2 and case 4. Case 2 had combined endometrial cancer, which could be associated with tuberous sclerosis complex (TSC). She was followed up for 22 months and neither recurrence nor metastasis was detected. Neither recurrence nor metastasis was found in case 3 for 33 months. However, the patient in case 4 died of multiple dissemination and multiple organs failures, 10 months after the second surgery. The patient in case 5 had the hysterectomy and left adnexal resection and in this case we had no data about her long-term outcomes. It is still challenging to detect and diagnose uterine PEComa clinically and no consensus or guidelines have been established regarding the treatment of this condition. More case studies are needed to enlighten the underlying mechanism and help optimize the therapies for this condition.

In the current object detection field, one of the fastest algorithms is the Single Shot Multi-Box Detector (SSD), which uses a single convolutional neural network to detect the object in an image. Although SSD is fast, there is a big gap compared with the state-of-the-art on mAP. In this paper, we propose a method to improve SSD algorithm to increase its classification accuracy without affecting its speed. We adopt the Inception block to replace the extra layers in SSD, and call this method Inception SSD (I-SSD). The proposed network can catch more information without increasing the complexity. In addition, we use the batch-normalization (BN) and the residual structure in our I-SSD network architecture. Besides, we propose an improved non-maximum suppression method to overcome its deficiency on the expression ability of the model. The proposed I-SSD algorithm achieves 78.6% mAP on the Pascal VOC2007 test, which outperforms SSD algorithm while maintaining its time performance. We also construct an Outdoor Object Detection (OOD) dataset to testify the effectiveness of the proposed I-SSD on the platform of unmanned vehicles.

This paper presents the methods we adopt for ICME2017 large scale 3D human activity analysis challenge in depth videos. There are two tasks including the segmented activity recognition and the untrimmed activity detection. We adopt a network structure comprised of two LSTM layers, a fully connected layer and a softmax layer. For the recognition task, we investigate several schemes to handle the inconsistency of subject number of different activities. For the detection task, we trim multi-scale segment parts from untrimmed videos and adopt a proposal network followed by a classification network.

Objective To compare the efficacy of metformin plus megestrol acetate (MA) with that of MA alone for treating endometrial atypical hyperplasia (EAH). Methods This pilot study included 16 EAH patients who met at least one metabolic syndrome (MS) criterion and received either adjunctive metformin plus MA (MET group) or MA monotherapy (MA group). Each patient in the MA group received 160 mg of MA daily, whereas patients in the MET group received the same dose of MA plus 0.5 g of metformin thrice daily. Treatment response was assessed by histological examination of dilation and curettage specimens obtained after 12 weeks of therapy. Results Each group had eight patients, and half of the patients in each group were diagnosed with MS. The complete response (CR) rate was 75% (6/8) in the MET group and 25% (2/8) in the MA group (p=0.105). Complications of MS did not affect the response rates in either group. In the MET group, 75% (3/4) of the patients had CR in the presence or absence of MS. In the MA group, 50% (2/4) of the patients with MS had CR, whereas no patient without MS had CR. No irreversible toxicities were observed. Conclusion Metformin plus MA may be a potential alternative therapy for treating EAH, and the MS status of patients may have no effect on the efficacy of metformin plus MA therapy.

To explore the relationship between metabolic abnormalities and DPE (disordered proliferative endometrium), EH (endometrial hyperplasia) and type I EC (endometrial cancer).We conducted a prospective cross-sectional study that lasted from September 2011 to September 2012 at the Obstetrics and Gynecology Hospital of Fudan University. 314 cases were enrolled, including 56 cases of DPE, 194 cases of EH and 25 cases of type I EC. 39 healthy female cases were collected as a control group. General information was collected, and blood tests, including blood lipids, OGTT (75-g oral glucose tolerance test) and insulin release tests were examined. Statistical analysis was performed using SPSS 19.0 (Chicago, USA), and 0.05 was chosen as the significance test level.The median (inter-quartile) age of the 314 study subjects was 44 (12) years, with the ages ranging from 21 to 75 years. Elevated insulin level was correlated with DPE, EH without/with atypia and EC. The risk increased when HOMA-IR (homeostasis model assessment-insulin resistance)≥ 2.95 (the lower limit of the top quartile of HOMA-IR distribution in non-diabetic patients); the OR (odds ratio) for DPE was 9.973 (95% CI (coefficient interval): 2.038-48.789, P=0.005), that for EH without atypia was 8.481 (95% CI:1.860-38.672, P=0.006), that for EH with atypia was 18.716 (95% CI: 3.091-113.335, P=0.001) and that for type I EC was 45.199 (95% CI: 5.886-347.065, P0.001). Opposite trends were observed for the QUICKI (Quantitative Insulin Sensitivity Check Index).Hyperinsulinemia is associated with DPE and EH without/with atypia, not only with type I EC, and it might be a key factor that initiates and promotes endometrial hyperplastic lesions.

We aimed to evaluate the value of immunohistochemical markers and serum CA125 in predicting the risk of lymph node metastasis (LNM) in women with endometrial cancer and to identify a low-risk group of LNM. The medical records of 370 patients with endometrial endometrioid adenocarcinoma who underwent surgical staging in the Obstetrics & Gynecology Hospital of Fudan University were collected and retrospectively reviewed. Immunohistochemical markers were screened. A model using serum cancer antigen 125 (CA125) level, the immunohistochemical markers progesterone receptor (PR) and Ki67 was created for prediction of LNM. A predicted probability of 4% among these patients was defined as low risk. The developed model was externally validated in 200 patients from Shanghai Cancer Center. The efficiency of the model was compared with three other reported prediction models. Patients with serum CA125 < 30.0 IU/mL, either or both of positive PR staining > 50% and Ki67 < 40% in cancer lesion were defined as low risk for LNM. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.82. The model classified 61.9% (229/370) of patients as being at low risk for LNM. Among these 229 patients, 6 patients (2.6%) had LNM and the negative predictive value was 97.4% (223/229). The sensitivity and specificity of the model were 84.6% and 67.4% respectively. In the validation cohort, the model classified 59.5% (119/200) of patients as low-risk, 3 out of these 119 patients (2.5%) has LNM. Our model showed a predictive power similar to those of two previously reported prediction models. The prediction model using serum CA125 and the immunohistochemical markers PR and Ki67 is useful to predict patients with a low risk of LNM and has the potential to provide valuable guidance to clinicians in the treatment of patients with endometrioid endometrial cancer.

Persistent unopposed estrogen stimulation is a central oncogenic mechanism driving the formation of type I endometrial cancer. Recent epidemiologic and clinical studies of endometrial cancer have also revealed a role for insulin resistance, clinically manifested by chronic inflammation. However, the role of inflammation in estrogen-driven endometrial cancer is not well characterized. In this study, we investigated the association between infiltrating macrophages and estrogen sensitivity in endometrial cancer. Evaluating tissue samples and serum from patients with precancerous lesions or endometrial cancer, we found that tissue macrophage infiltration, but not serum estradiol levels, correlated positively with endometrial cancer development. Furthermore, IL4/IL13-induced CD68+CD163+ macrophages enhanced the proliferative effects of estradiol in endometrial cancer cells by upregulating estrogen receptor alpha (ERα), but not ERβ. Mechanistic investigations revealed that CD68+CD163+ macrophages secreted cytokines, such as IL17A, that upregulated ERα expression through TET1-mediated epigenetic modulation of the ERα gene. Overall, our findings show how cytokines produced by infiltrating macrophages in the endometrial microenvironment can induce epigenetic upregulation of ERα expression, which in turn sensitizes endometrial cells to estrogen stimulation. The concept that inflammation-induced estrogen sensitivity in the endometrium acts as a driver of type I endometrial cancer has implications for infiltrating macrophages as a prognostic biomarker of progression in this disease setting. Cancer Res; 76(6); 1354–66. ©2016 AACR.

The purpose of the study was to explore the role and mechanism of ataxia-telangiectasia mutated (ATM) protein in endometrial carcinogenesis. A reverse-phase protein array (RPPA) was used to analyze the expression of ATM signal pathway proteins in Ishikawa and progesterone-insensitive Ishikawa. ATM expression was detected in endometrium specimens by immunohistochemistry, including 8 cases with proliferative endometrium, 6 cases with secretory endometrium, 10 cases with simple hyperplasia (SH), 13 cases of complex hyperplasia (CH), 11 cases of endometrial atypical hyperplasia (EAH), and 83 cases with type I endometrial cancer. The relationship between ATM expression and other clinicopathological indicators was also examined in type I endometrial cancer patients. The mechanisms of ATM were explored in vitro with the endometrial cell lines Ishikawa and RL95-2. A cell counting kit-8 (CCK-8) test and Western blot analysis were performed to test proliferation and protein expression. Statistical analysis was performed with SPSS19.0. The significance level was set at 0.05. ATM was increased with medroxyprogesterone acetate (MPA) stimulation in Ishikawa in RPPA. ATM expression gradually decreased in endometrial hyperplasic lesions compared with the normal proliferative and secretory endometrium and was the lowest in type I endometrial cancer. ATM expression was negatively correlated with pathological grades in type I endometrial cancer. In vitro, ATM silencing retarded proliferation inhibition in Ishikawa and RL95-2 treated with MPA. ATM silencing could down-regulate the MPA-stimulated signal proteins, including Chk2, P53, and caspase-3 in vitro. MPA might exert its role through activating the ATM-associated pathway, ATM-Chk2-P53-caspase-3 (active), preserving normal endometrium and protecting it from malignancies. ATM might be a promising indicator for endometrial hyperplasia and cancer.