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Most EEC cases are associated with activities of the mTOR pathway, which regulates protein synthesis, cell growth and autophagy. While Up-Frameshift 1(UPF1) is a key protein factor in the nonsense-mediated mRNA degradation pathway (NMD), its role in carcinogenesis of EEC remains unclear. In this study, we first evaluated the expression level of UPF1 in EEC tissues and cell lines. Then, we investigated the effect of UPF1 on cellular function and mTOR signaling pathway; these effects were further validated in vivo. Finally, its effect on autophagy was evaluated by western blot and GFP-mRFP-LC3 staining. UPF1 expression in the EEC tissue samples was significantly higher than that of matched normal tissue samples. Overexpression of UPF1 promoted migration and invasion of EEC cells. Conversely, depletion of UPF1 suppressed migration and invasion of EEC cells. In addition, overexpression of UPF1 increased the in vivo growth of our EEC xenograft tumors. Finally, UPF1 increased the activity of the mTOR/P70S6K/4EBP1 signaling pathway and inhibited autophagy in EEC cells. These findings suggest that UPF1 functions as an oncogene to promote EEC carcinogenesis. Our findings propose UPF1 as a new potential therapeutic target for EEC.

Background and objectives: The precise grading and characterization of cervical intraepithelial neoplasia (CIN) has been the focus of pathologists for a long time. This study aimed to explore known strategies for the grading of CINs.Methods: After routine H&E review, 85 lesions graded CIN 1, 2, or 3 were investigated primarily by HPV RNAscope to detect HR-HPV and LR-HPV, in combination with an HPV-DNA test and P16/Ki67 immunohistochemistry (IHC). Then, the 85 cases were divided into a control group (49 cases) and a test group (36 cases). The former consisted of cases with consistency between morphology, HPV DNA detection and P16/Ki67 IHC. We used them to evaluate HPV RNA distribution patterns in CINs of different grades. The latter were ambiguous cases in which pathologists could not confirm the diagnosis because of inconsistencies between morphology, HPV DNA detection and P16/Ki67 IHC. We reassessed them by comparison to the pattern in the control group.Results: The expression patterns of HPV mRNA signals were different in different CIN lesions. LSIL/CIN1 lesions were mostly expressed in superficial epithelium with diffuse clustered nuclear or cytoplasmic staining; HSIL/CIN2 were characterised by nuclear/cytoplasmic punctate or diffuse cluster nuclear staining in the mid-surface layer, and scattered nuclear/cytoplasmic punctate staining in basal and parabasal cells; whereas HSIL/CIN3 showed full-thickness nucleus/cytoplasmic scattered staining with a punctate pattern. According to the staining pattern, we corrected the diagnosis of 22 cases (22/36, 61.1%). Conclusion: Because of its distinct location pattern, HPV RNAscope has obvious advantages over the HPV-DNA test, and combined with P16/Ki67 IHC, it can help pathologists correctly grade CIN. In addition, it can effectively discriminate true CIN from normal or CIN mimic lesions, such as immature squamous metaplasia, atrophy, and inflammatory/reactive changes. Therefore, HPV RNAscope is a valuable auxiliary diagnostic test to avoid the overtreatment and undertreatment of CIN lesions.

Our previous study demonstrated the role of family with sequence similarity 83, member B (FAM83B) in endometrial cancer tumorigenesis and metastasis. FAM83B is involved in epithelial-to-mesenchymal transition (EMT). However, the regulatory network of EMT, which promotes endometrial cancer cell metastasis, involving microRNAs (miRNAs/miRs) and FAM83B, has not been elucidated. To investigate the potential mechanism underlying miR-199a/b-5p in endometrial cancer, the effect of miR-199a/b-5p and its targeted FAM83B gene on the biological behaviour of endometrial cancer cells was assessed. The Gene Expression Omnibus dataset analysis results revealed that the expression levels of 150 miRNAs in non-cancerous endometrial tissues were upregulated compared with those in endometrial cancer tissues. TargetScan predicted that the nucleotides 672–679 of FAM83B 3′-untranslated region (UTR) were the target sites of miR-199a/b-5p. The differentially expressed miRNAs were enriched in several Kyoto Encyclopedia of Genes and Genomes pathways. Reverse transcription-quantitative PCR analysis revealed that the expression levels of miR-199a/b-5p in the endometrial non-cancerous cell lines were significantly upregulated compared with those in the six endometrial cancer cell lines. miR-199a/b-5p inhibited the EMT signaling pathway by regulating the expression levels of E-cadherin, N-cadherin, Snail, α-smooth muscle actin, vimentin and Twist. This suggested that miR-199a/b-5p inhibited endometrial cancer cell proliferation and migration through the inhibition of the EMT signaling pathway. Furthermore, the nucleotides 672–679 of the FAM83B 3′-UTR were demonstrated to be the binding site of miR-199a/b-5p. These results suggested that miR-199a/b-5p inhibited endometrial cancer cell proliferation and metastasis by targeting the 3′-UTR of FAM83B, which is involved in the EMT signaling pathway.

Background Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer that accounts for up to 40% of endometrial cancer deaths, creating an urgent need for prognostic biomarkers. Methods USC RNA-Seq data and corresponding patients’ clinical records were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Univariate cox, Lasso, and Multivariate cox regression analyses were conducted to forge a prognostic signature. Multivariable and univariable cox regression analysis and ROC curve evaluated the prediction efficiency both in the training and testing sets. Results We uncovered 1385 genes dysregulated in 110 cases of USC tissue relative to 113 cases of normal uterine tissue. Functional enrichment analysis of these genes revealed the involvement of various cancer-related pathways in USC. A novel 4-gene signature (KRT23, CXCL1, SOX9 and ABCA10) of USC prognosis was finally forged by serial regression analyses. Overall patient survival (OS) and recurrence-free survival (RFS) were significantly lower in the high-risk group relative to the low-risk group in both the training and testing sets. The area under the ROC curve of the 4-gene signature was highest among clinicopathological features in predicting OS and RFS. The 4-gene signature was found to be an independent prognostic indicator in USC and was a superior predictor of OS in early stage of USC. Conclusions Our findings highlight the potential of the 4-gene signature as a guide for personalized USC treatment.

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Our previous study demonstrated the role of family with sequence similarity 83, member B (FAM83B) in endometrial cancer tumorigenesis and metastasis. FAM83B is involved in epithelial-to-mesenchymal transition (EMT). However, the regulatory network of EMT, which promotes endometrial cancer cell metastasis, involving microRNAs (miRNAs/miRs) and FAM83B, has not been elucidated. To investigate the potential mechanism underlying miR-199a/b-5p in endometrial cancer, the effect of miR-199a/b-5p and its targeted FAM83B gene on the biological behaviour of endometrial cancer cells was assessed. The Gene Expression Omnibus dataset analysis results revealed that the expression levels of 150 miRNAs in non-cancerous endometrial tissues were upregulated compared with those in endometrial cancer tissues. TargetScan predicted that the nucleotides 672–679 of FAM83B 3′-untranslated region (UTR) were the target sites of miR-199a/b-5p. The differentially expressed miRNAs were enriched in several Kyoto Encyclopedia of Genes and Genomes pathways. Reverse transcription-quantitative PCR analysis revealed that the expression levels of miR-199a/b-5p in the endometrial non-cancerous cell lines were significantly upregulated compared with those in the six endometrial cancer cell lines. miR-199a/b-5p inhibited the EMT signaling pathway by regulating the expression levels of E-cadherin, N-cadherin, Snail, α-smooth muscle actin, vimentin and Twist. This suggested that miR-199a/b-5p inhibited endometrial cancer cell proliferation and migration through the inhibition of the EMT signaling pathway. Furthermore, the nucleotides 672–679 of the FAM83B 3′-UTR were demonstrated to be the binding site of miR-199a/b-5p. These results suggested that miR-199a/b-5p inhibited endometrial cancer cell proliferation and metastasis by targeting the 3′-UTR of FAM83B, which is involved in the EMT signaling pathway.

Endometrioid endometrial carcinoma (EEC) is one of the most common malignant gynecologic tumors worldwide. Most EEC cases are associated with activities of the mTOR pathway, which regulates protein synthesis, cell growth and autophagy. While Up-Frameshift 1(UPF1) is a key protein factor in the nonsense-mediated mRNA degradation pathway (NMD), its role in carcinogenesis of EEC remains unclear. In this study, we first evaluated the expression level of UPF1 in EEC tissues and cell lines. Then, we investigated the effect of UPF1 on cellular function and mTOR signaling pathway; these effects were further validated in vivo. Finally, its effect on autophagy was evaluated by western blot and GFP-mRFP-LC3 staining. UPF1 expression in the EEC tissue samples was significantly higher than that of matched normal tissue samples. Overexpression of UPF1 promotes migration and invasion of EEC cells. Conversely, depletion of UPF1 suppresses migration and invasion of EEC cells. In addition, overexpression of UPF1 increased the in vivo growth of our EEC xenograft tumor. Finally, UPF1 increased the activity of the mTOR/P70S6K/4EBP1 signaling pathway and inhibited autophagy in EEC cells. These findings suggest that UPF1 functions as an oncogene to promote EEC carcinogenesis. Our findings propose UPF1 as a new potential therapeutic target for EEC. Funding Statement: This study was supported by the Guangdong Science and Technology Department (No.2019A1515012194), The Health and Family Planning Commission of Guangzhou Municipality (No.201707010425)，and Lin He’s Academician Workstation of New Medicine and Clinical Translation. Declaration of Interests: The all authors declare that they have no competing interests. Ethics Approval Statement: All patients provided informed consent, and the study was approved by the ethics committee of Third Affiliated Hospital of Guangzhou Medical University.

Background Ciliated muconodular papillary tumors (CMPTs) is a descriptive diagnostic term which indicates the composition of tumor cells (ciliated and mucous cells) and the pattern of growth (papillary). It is shown that the proportion of the various cells is different and the papillary structure is not necessary for diagnosis of this tumor. As a result, several scholars proposed that CMPT is a proximal-type bronchiolar adenoma (BA), a possibility which expanded the spectrum of CMPT. These morphological variations therefore introduced major challenges when diagnosing CMPTs. Case presentation Multiple small nodules in both lungs were found in a 79-year-old female patient. A frozen section of the nodules was performed. Grossly, the nodules were jelly-like with clear boundaries and had a maximum diameter of approximately 4 mm. Microscopic examination showed glandular ducts, papillary, and even micropapillary structures. The cavities were lined by columnar and mucous cells. A conspicuous mucin pool was observed in low-power fields, in addition to floating tumor cells in the mucin pool. Based on these findings, atypical adenomatous hyperplasia of the lung was reported as the intraoperative rapid diagnosis, and the surgeon performed a lobectomy in the patient. A typical hematoxylin-eosin (HE) stain showed that the tumor consisted of three kinds of cells in different proportions, including ciliated columnar, mucous, and basal cells which were confirmed by CK5/6 and P63 immunohistochemistry staining. BRAF V600E protein was expressed in the tumor and at the same time the tumor was shown to harbor the BRAF gene mutation. Conclusion We report a classic CMPT with a BRAF mutation that expressed BRAF protein. Classic lesions are easy to identify, whereas in cases of morphological variants the key to diagnosis of the disease is the diversity of cell components and the presence of basal cells.

Nasopharyngeal carcinoma (NPC), is one of the most common malignant tumor in southern China and southeast Asia. MYH10 is a coding gene of the NMMHC-IIB protein. Previous studies have shown that MYH10 expression was up-regulated in breast cancer, glioma and meningioma. Moreover, it was targeted by miR200 family. However, no relevant studies have been found in NPC. In present study, we found in 48 NPC specimens, MYH10 level was lower in most cancer areas than that in the adjacent normal tissue. Moreover, the depletion of MYH10 can promote the migration and invasion of NPC. In addition, we demonstrated that miR-200a has the strongest regulation to MYH10 among miR-200 family. miR-200a mimics could decrease MYH10 expression, while miR-200a inhibitor increase MYH10 expression. Next, we found that miR-200a bound directly to MYH10 using Dual-luciferase reporter. Finally, it was demonstrated that siMYH10 could reverse the effect of miR-200a inhibitor on NPC cell migration and invasion. Taken together, it can be concluded that MYH10 is lowly expressed in NPC compared with adjacent tissues, and the loss of MYH10 can promote the migration and invasion of NPC cells; Among the miR-200 family, miR-200a has the strongest regulatory effect on MYH10; MYH10 is a direct target gene of miR200a, and miR200a targets MYH10 to regulate the migration and invasion of NPC cells.

Family with sequence similarity 83 member B (FAM83B) has been recently identified as an oncogene involved in the development of various human cancers. However, the role of FAM83B in endometrial cancer tumorigenesis and metastasis is unclear. In this study, we found that the expression of FAM83B was upregulated in endometrial cancer tissues and cell lines. FAM83B expression in endometrial cancer tissues was significantly higher than that in normal tissues and higher FAM83B expression was closely related to poorly survival rate according to TCGA analysis. Moreover, FAM83B expression was correlated with International Federation of Gynecology and Obstetrics (FIGO)stage and myometrial invasion but had no significant correlation with age or histological grade. FAM83B knockdown inhibited endometrial cancer cell proliferation, migration, and invasion arrested the cell cycle at the G1/S stage and promoted apoptosis. FAM83B knockdown also inhibited endometrial cancer growth and lung metastasis in vivo. FAM83B knockdown silenced the PI3K/AKT/mTOR pathway and promoted autophagy. Furthermore, activation of the PI3K/AKT/mTOR pathway reversed FAM83B knockdown-induced autophagy promotion and inhibition of proliferation, migration, and invasion in endometrial cancer cells. Taken together, these results indicate that FAM83B promotes endometrial cancer cell proliferation and metastasis by inhibiting autophagy via activating the PI3K/AKT/mTOR pathway.

Endometrioid endometrial carcinoma (EEC) is the most common gynecologic malignancy around the world. Epithelial-to-mesenchymal transition (EMT) is a core process during EEC cell invasion. The abnormal expression of the long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) or miR-200 family members were shown to facilitate EMT in multiple human cancers, but the regulatory mechanism by which MALAT1 and miR-200 act remains unknown. Previous studies have shown that miR-200 family members are enriched in EEC as well as melanoma and some ovarian carcinomas. In the present study, we first showed that miR-200c levels were higher in most EEC specimens than in non-tumor tissues, while MALAT1 levels were lower. Moreover, we found that miR-200c bound directly to MALAT1 using luciferase reporter and qRT-PCR assays. MALAT1 and miR-200c are reciprocally repressed, and TGF-β increased MALAT1 expression by inhibiting miR-200c. When the interaction between miR-200c/MALAT1 was interrupted, the invasive capacity of EEC cells was decreased and EMT markers expression were altered in vitro. A xenograft tumor model was used to show that targeting the miR-200c/MALAT1 axis inhibited EEC growth and EMT-associated protein expression in vivo. In summary, miR-200c/MALAT1 axis is a target with therapeutic potential in EEC. However, different expression model of miR-200c and MALAT1 in EEC with that in other organ carcinomas needs further mechanism researches.

Endometrial carcinoma is one of the most common malignancies in the female reproductive system. It is well-known that estrogen plays an important role in the pathogenesis of endometrioid endometrial carcinoma (EEC), and induces the cancer suppressor gene PTEN deletion. However, how estrogen affects PTEN expression remains unknown. In the present study, we found in 40 EEC specimens, miR-200c level was higher in most cancer areas than that in the adjacent normal endometrium, while PTEN and PTENP1 were lower. Moreover, the expression of PTEN/PTENP1 and miR-200c also showed a converse relationship in EEC cell lines. In addition, we demonstrated that miR-200c bound directly to PTEN and PTENP1, and PTENP1 could reverse miR-200c inhibition function to PTEN using a dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays. Next, 17β-estradiol (E2) treatment could improve miR-200c and drop the PTEN level, which caused a consequential increase of the phospho-PI3K-AKT pathway genes. When we stably knocked down estrogen receptor α (ERα) expression in the EEC cell line, the effects of E2 on miR-200c and PTEN declined. In addition, it was demonstrated that E2 might modulate cell proliferation, migration and invasion relying on the expression of miR-200c. Taken together, it can be concluded that estrogen improves the miR-200c level by combining with ER, PTENP1 and PTEN could be inhibited by miR-200c, and then activate the PI3K-AKT pathway. This work provided a new mechanism of EEC development and a new potential therapeutic target.

O estudo que aqui apresento estende-se pelo espaço de duzentos anos, decorrente nos séculos XVI e XVII, tempo em que chegaram mais portugueses, nomeadamente os jesuítas por motivos religiosos, ao Império do Meio, e se registaram numerosos escritos assinaláveis sobre aquela terra oriental, nos quais, incluíam inúmeras descrições importantes sobre os letrados chineses das dinasti as Ming (1368-1644) e Qing (1644-1912) da China continental. No que respeita às primeiras imagens dos letrados chineses, abordar-se-ão os primeiros textos portugueses que se referem àclasse letrada, logo a seguir aos primeiros contactos diretos com a China, em 1513, e até 1583. Serão tratados nomeadamente os trabalhos do cativo de Cantão, D. Jerónimo Osório, Fernão Lopes de Castanheda, Galiote Pereira, Frei Gaspar da Cruz, Fernão Mendes Pinto, entre outros. Atestar-se-áo nascimento de uma imagem francamente positiva dos letrados chineses, que leva a que os padres jesuítas modifiquem a sua estratégica de missionação relativamente àChina, com resultados francamente positivos. Analisam-se a seguir os avanços na missão jesuíta da China, que se desenvolve a partir de 1583, graças a um conhecimento cada vez mais aprofundado da língua e da cultura chinesas. O sucesso de Matteo Ricci e dos seus confrades europeus estáligado precisamente ao relacionamento que estabelecem com os letrados chineses, optando por uma forma de missionação mais elitista. Analisam -se as notícias transmitidas pelos padres jesuítas sobre os letrados chineses, nomeadamente as suas atitudes perante as culturas europeias, àfécristã, aos padres ocidentais, entre outros. Além disso, explorará a imagem dos letrados chineses nas obras dos três missionários jesuítas que deixaram as mais significativas descrições da China: Álvaro Semedo, António de Gouveia e Gabriel de Magalhães. As informações jesuítas serão confrontadas com materiais chinesas, permitindo verificar o respetivo rigor. O trabalho inclui ainda um capítulo dedicado a Xu Guangqi, o famoso «Doutor Paulo» das fontes jesuítas, um dos primeiros letrados chineses a converter-se ao Cristianismo. O Doutor Paulo foi um dos grandes apoiantes da missão jesuíta, e será tomado como paradigma do «letrado cristão», analisando -se a sua formação, as atividades a que se dedicou e, sobretudo o seu apoio àmissão jesuíta na Chin a. De qualquer modo, do ponto de vista cultural, os portugueses apresentaram a classe letrada da China Ming e Qing de forma relativamente correta. As suas descrições, embora não completas e com uma tonalidade religiosa, não perderam a essência do carácter dos letrados antigos. Graças aos relatos dos padres missionários, despertou um grande interesse e uma especial atenção entre as classes cultas ocidentais da época, constituindo mesmo um tema privilegiado na literatura europeia dedicada à Ásia, em geral, e à China, em especial. Por outro lado, as considerações dos jesuítas sobre os letrados e as obras confucionistas, contribuíram muito para a divulgação da cultura chinesa, na Europa culta, ampliando grandemente a visão dos europeus sobre a ideologia e a civilização chinesas, além de renovar o saber e a visão tradicionais da Europa, de então, sobre a China. The study hereby presented covers over two hundred years’ history, traced back to the sixteenth and seventeenth centuries. At that time, many Portuguese had arrived in the Middle Kingdom, among whom the Jesuits who came for religious purposes. There were numerous important writings about that eastern land, including countless significant descriptions of literati of the Ming (1368-1644) and Qing (1644-1912) dynasties of China. Regarding the first images of Chinese literati, the first Portuguese texts upon the Chinese literati, followed immediately after their first direct contacts with China from 1513 and until 1583, will be discussed, in particular, the works of the captive of Cantão, D. Jerónimo Osório, Fernão Lopes de Castanheda, Galiote Pereira, Frei Gaspar da Cruz, Fernão Mendes Pinto, among others. It witnessed the birth of a frankly positive image of Chinese literati, which made the Jesuit priests to modify their missionary strategy towards China, with frankly positive results. The progress of the Jesuit mission in China, which began in 1583, is being analyzed, thanks to an ever deeper knowledge of the Chinese language and culture. The success of Matteo Ricci and his European confreres was linked exactly to the relationship they established with Chinese scholars, and they chose a more elitist form of missionary. The news about Chinese literati transmitted by the Jesuit priests, especially their attitudes towards European cultures, the Christian faith, the Western priests, among other things, were also analysed in the thesis. In addition, the image of Chinese scholars in the works of the three Jesuit missionaries: Álvaro Semedo, António de Gouvei a and Gabriel de Magalhães, who left the most significant descriptions of China, will be explored, in the thesis. The Jesuit information will be confronted with Chinese materials, allowing to verify its rigor. The thesis also includes a chapter dedicated to Xu Guangqi, the famous "Doctor Paulo" of the Jesuit sources, who was one of the first Chinese literati to convert to Christianity. Dr. Paulo was one of the great supporters of the Jesuit mission, and will be taken as a paradigm of the "Christian scholar", analyzing his formation, the activities he dedicated himself and, above all, his support for the Jesuit mission in China.

Background Although cases of cervical squamous cell carcinoma metastatic to the ovary have been previously documented, we report the first case of superficially invasive squamous cell carcinoma metastatic to the ovary. Case presentation A 45-year-old woman with a two-year history of ovarian endometriosis confirmed by ultrasound underwent oophorectomy. On microscopic examination, a focus of malignant stratified epithelium, initially interpreted as transitional cell carcinoma, was identified within the endometriotic cyst wall. Examination of the hysterectomy specimen revealed superficially invasive squamous carcinoma of the cervix. In addition, two triploid, CD45-negative cells were detected during the analysis of the peripheral blood for circulating tumor cells (CTC). High-risk HPV was detected on the sections of endometriosis containing cancerous area by using hybrid capture 2 assay, supporting the diagnosis of metastatic squamous cell carcinoma originating from the uterine cervix. Conclusion This is the first report of superficially invasive squamous cell carcinoma metastatic to the ovary. Such finding could be misdiagnosed as primary ovarian transitional cell carcinoma, squamous cell carcinoma originating from metaplastic epithelium within endometriosis, or squamous cell carcinoma arising in a teratoma.