Erratum: [Corrigendum] MicroRNA­23a inhibits endometrial cancer cell development by targeting SIX1.

[This corrects the article DOI: 10.3892/ol.2019.10694.].

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Large pelvic mass arising from the cervical stump: A case report.

BACKGROUND: A large cervical cyst with a cervical high-grade squamous intraepithelial lesion arising from the cervical stump is rare. After supracervical hysterectomy, there is a risk of various lesions occurring in the cervical stump. We review the types and characteristics of cervical stump lesions and compare total hysterectomy with subtotal hysterectomy. Gynecologists should choose the most suitable surgical method based on both the patient's condition and wishes. If the cervix is retained, patients require a close follow-up. CASE SUMMARY: A 57-year-old woman was admitted to the Gynecology Department for a large pelvic mass. Her chief complaint was abdominal distention for two months. She had undergone subtotal supracervical hysterectomy for leiomyoma 14 years prior. Abdominal ultrasonography detected a 9.1 cm × 8.5 cm × 8.4 cm anechoic mass with silvery fluid in the pelvic cavity and high-risk human papilloma virus 53 (HPV53) was positive. The admission diagnosis we first considered was a pelvic mass mimicking carcinoma of the cervical stump. We performed a laparotomy and a rapid frozen biopsy was suggestive of a fibrous cyst wall coated with a high squamous intraepithelial lesion. The pelvic mass was removed, and a bilateral adnexectomy was implemented. Final pathology confirmed that the pelvic mass was a large inflammatory cyst with a cervical high-grade squamous intraepithelial lesion. After successful intervention, the patient was discharged one week after surgery and there was no recurrence of the vaginal stump at 43 mo. CONCLUSION: When addressing benign uterine diseases, gynecologists should pay adequate attention to retaining the cervix. If the cervix is retained, patients require a close follow-up.

Pre-eclampsia with new-onset systemic lupus erythematosus during pregnancy: A case report.

BACKGROUND: New-onset systemic lupus erythematosus (SLE) during pregnancy and in the postpartum period is rare, especially when complicated with pre-eclampsia, which is difficult to diagnose accurately. Here, we report a patient with new-onset SLE and antiphospholipid syndrome during pregnancy, which presented as pre-eclampsia at admission. CASE SUMMARY: A 28-year-old primigravid woman was admitted to our hospital in the 27th wk of gestation with the primary diagnosis of severe pre-eclampsia. Although spasmolysis and antihypertensive therapy were administered since admission, the 24-h proteinuria of the 2nd day after admission reached 10311.0 mg. In the 47th h of admission, immunologic examinations revealed increased levels of anti-double stranded DNA antibody, anti-nuclear antibody, anti-cardiolipin antibody, anti-Sjögren's syndrome-related antigen A antibody and anti-nucleosome antibody and decreased levels of complement C3 and C4. One hour later, ultrasonography of the lower limbs showed thrombus of the bilateral popliteal veins. The diagnosis of SLE and antiphospholipid syndrome was indicated. In the 54th h, the patient manifested with convulsion, dyspnea and blurred vision. Ten hours later, intrauterine death was revealed by ultrasonography. Emergent surgery consisting of inferior vena cava filter implantation and subsequent cesarean section was performed. Following glucocorticoid and anticoagulation therapy after delivery, the patient had an optimal response with improvements in symptoms and immunological markers. CONCLUSION: Obstetricians should be aware of the symptoms and immunological examination results to distinguish pre-eclampsia and underlying SLE for optimal pregnancy outcomes.

MicroRNA-23a inhibits endometrial cancer cell development by targeting SIX1.

The present study focused on exploring the inhibitory mechanism of microRNA (miR)-23a in endometrial cancer. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to investigate miR-23a expression in endometrial tissues and endometrial cancer cells. A colony formation assay using crystal violet staining was performed to compare cell proliferation, while wound-healing and Transwell assays were performed to compare cell migration and invasion. Subsequently, bioinformatics and a luciferase reporter gene assay were used to investigate the effect of miR-23a on sine oculis homeobox homolog 1 (SIX1) expression, and the biological function of SIX1 was analyzed. Additionally, a nude mouse tumorigenicity assay was performed to test the inhibitory effect of miR-23a and Taxol® therapy in endometrial cancer. Finally, immunohistochemistry and RT-qPCR were used to explore the association between miR-23a and SIX1 expression in endometrial cancer tissues. miR-23a was underexpressed in endometrial cancer tissues compared with in para-carcinoma tissues, and the overexpression of miR-23a inhibited proliferation and invasion of endometrial cancer cells. Furthermore, SIX1 was demonstrated to be a downstream target of miR-23a, and miR-23a reduced SIX1 expression. Additionally, SIX1 inversely promoted cell proliferation, migration and invasion. In addition, the effects of reduced cell proliferation and increased cell invasion following miR-23a overexpression could be reversed by adding SIX1 to in vitro culture. Furthermore, the inhibitory effect of miR-23a and Taxol therapy, which reduced SIX1 expression in endometrial cancer, was demonstrated in vivo. Finally, a negative association between miR-23a and SIX1 expression was demonstrated in endometrial cancer tissues. The results of the present study revealed that miR-23a may inhibit endometrial cancer development by targeting SIX1.

The Increased PTK7 Expression Is a Malignant Factor in Cervical Cancer.

Cervical cancer is one of the most common malignant neoplasms in gynecology. Protein tyrosine kinase 7 (PTK7) with an inactive kinase domain is an important regulator of multiple Wnt pathways under normal and various pathological conditions and overexpressed in various tumors; however, the clinical and biological significance of PTK7 in cervical cancer is still unknown. In the present study, the protein expression level of PTK7 was detected in clinical cervical cancer patient samples, and the relationship between PTK7 expression and clinicopathological features was analyzed. In addition, the Kaplan-Meier method was performed to estimate the overall survival (OS) and progression-free survival (PFS) of patients to investigate the clinicopathological significance of PTK7 expression. Functional assays demonstrated that knocking down PTK7 might inhibit the ability of cancer cells to proliferate and invade or migrate, both in vivo and in vitro. Thus, PTK7 might serve as a potential target for cervical cancer.

Characterization of embryonic stem cell model of polycystic ovary syndrome.

The aims of this study are to establish an embryonic stem (ES) cell model of polycystic ovary syndrome and to characterize this ES cell line. ES cells were isolated and cultured from 322 wasted fertilized embryos from polycystic ovary syndrome (PCOS) patients in vitro. They were also characterized by development and differential markers. ES cells from PCOS subject present normal development profile with ES-specific markers such as OCT-4 and SSEA-4. These ES cells can also differentiate into three germ layer derivatives and form teratomas in vivo. ES cells from PCOS patients pose development and differentiation potentials as you would expect of cells from non-PCOS patients; therefore, they can be used as a cellular model to study the pathology of PCOS.

Cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are believed to play an essential role in cancer initiation and development. However, little research has been undertaken to evaluate the role of CAFs in endometrial cancer (EC) progression. We aim to detect the functional contributions of CAFs to promote progression of EC. METHODS: Stromal fibroblasts were isolated from endometrioid adenocarcinomas and normal endometrial tissues. The conditioned media of cultured CAFs and normal fibroblasts (NFs) were collected to detect the level of stromal cell-derived factor-1alpha (SDF-1α), macrophage chemoattractant protein-1 (MCP-1), migration inhibitory factor (MIF), colony stimulating factor-1 (CSF-1), and interleukin-1 (IL-1) by ELISA. The CAFs or NFs were cocultured with EC cell lines to determine the proliferation, migration, and invasion by MTT assays and transwell chambers. Xenograft models were used to observe tumor growth. Matrix metalloproteinases (MMP)-2 and MMP-9 activity was evaluated by zymography. AMD3100 (a chemokine receptor 4 (CXCR4) antagonist) was used to block the SDF-1/CXCR4 axis. Neutralizing antibodies were used to detect PI3K/Akt and MAPK/Erk pathways by western blotting. SDF-1α and CXCR4 expressions were analyzed in xenotransplanted tumors and 348 cases by immunohistochemistry. RESULTS: CAFs promoted proliferation, migration, and invasion as well as in vivo tumorigenesis of admixed EC cells significantly more than NFs by secreting SDF-1α. These effects were significantly inhibited by AMD3100. CAFs promoted EC progression via the SDF-1α/CXCR4 axis to activate the PI3K/Akt and MAPK/Erk signalings in a paracrine-dependent manner or increase MMP-2 and MMP-9 secretion in an autocrine-dependent manner. SDF-1α and CXCR4 expression upregulation accompanied clinical EC development and progression. High SDF-1α expression levels were associated with deep myometrial invasion, lymph node metastasis, and poor prognosis in EC. CONCLUSIONS: Our data indicated that CAFs derived from EC tissues promoted EC progression via the SDF-1/CXCR4 axis in a paracrine- or autocrine-dependent manner. SDF-1α is a novel independent poor prognostic factor for EC patients' survival. Targeting the SDF-1/CXCR4 axis might provide a novel therapeutic strategy for EC treatment.

In vitro fertilization complicated by rupture of tubo-ovarian abscess during pregnancy.

OBJECTIVE: Pelvic abscess during pregnancy is an uncommon complication, but can lead to adverse perinatal outcomes during pregnancy. CASE REPORT: We present a patient who developed rupture of a tubo-ovarian abscess during pregnancy following in vitro fertilization and embryo transfer. Thirty-eight reported cases are reviewed, and transvaginal oocyte retrieval, genital tract infections, endometrioma, and previous pelvic surgery are considered as risk factors for pelvic abscess during pregnancy. CONCLUSION: Prolonging gestational duration when an infection situation is allowed is the principle of treatment.

Metabolomic analysis revealed the role of DNA methylation in the balance of arachidonic acid metabolism and endothelial activation.

Arachidonic acid (AA) metabolism plays an important role in vascular homeostasis. We reported that DNA hypomethylation of EPHX2 induced a pro-inflammatory response in vascular endothelial cells (ECs). However, the change in the whole AA metabolism by DNA methylation is still unknown. Using a metabolomic approach, we investigated the effect of DNA methylation on the balance of AA metabolism and the underlying mechanism. ECs were treated with a DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AZA), and AA metabolic profiles were analyzed. Levels of prostaglandin D2 (PGD2) and thromboxane B2 (TXB2), metabolites in the cyclooxygenase (COX) pathway, were significantly increased by 5-AZA treatment in ECs resulting from the induction of PGD2 synthase (PTGDS) and thromboxane A synthase 1 (TBXAS1) expression by DNA hypomethylation. This phenomenon was also observed in liver and kidney cell lines, indicating a universal mechanism. Pathophysiologically, homocysteine, known to cause DNA demethylation, induced a similar pattern of the change of AA metabolism. Furthermore, 5-AZA activated ECs, as evidenced by the upregulation of adhesion molecules. Indomethacin, a COX inhibitor, reversed the effects of 5-AZA on the levels of PGD2 and TXB2, EC activation and monocyte adhesion. In vivo, the plasma levels of PGD2 and TXB2 and the expression of In vivo PTGDS and TBXAS1 as well as adhesion molecules were increased in the aorta of the mice injected with 5-AZA. In conclusion, using a metabolomic approach, our study uncovered that DNA demethylation increased AA metabolites PGD2 and TXB2 by upregulating the expression of the corresponding enzymes, which might contribute to the DNA hypomethylation-induced endothelial activation.

Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer.

Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This "paradox" can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.

Contrast-enhanced MRI in preoperative assessment of myometrial and cervical invasion, and lymph node metastasis: diagnostic value and error analysis in endometrial carcinoma.

OBJECTIVE: To determine the ability of contrast-enhanced magnetic resonance imaging to predict myometrial invasion, cervical invasion, and pelvic lymph node metastasis in endometrial carcinoma and to analyze factors that lead to errors in this identification. DESIGN: A retrospective study. SETTING: University general hospital. POPULATION: A total of 167 women diagnosed with endometrial carcinoma. METHODS: All patients received a preoperative contrast-enhanced magnetic resonance imaging scan. Histopathological findings were used as the definitive diagnosis. MAIN OUTCOME MEASURES: The results were compared with histopathological findings, factors that make accurate assessment of myometrial invasion, cervical invasion, and pelvic lymph node metastasis difficult by contrast-enhanced magnetic resonance imaging were analyzed. RESULTS: The sensitivity, specificity, diagnostic accuracy, positive predictive values, and negative predictive values of contrast-enhanced magnetic resonance imaging were 90.9, 91.8, 91.6, 73.2 and 97.6%, respectively, for identifying deep myometrial invasion; 84.2, 96.0, 94.6, 72.7 and 97.9%, respectively, for identifying cervical invasion; and 45.0, 91.2, 85.6, 40.9 and 92.4%, respectively, for identifying pelvic lymph node metastasis. The main causes of error in contrast-enhanced magnetic resonance imaging were myomas, cornual lesions, deep myometrial invasion, large tumor size, non-endometrioid tumor type, and lower tumor grade. CONCLUSION: Contrast-enhanced magnetic resonance imaging has a high accuracy and a low tendency to produce false-negative predictive values. Gynecological oncologists should combine the imaging data and clinical information to make therapeutic decisions and avoid diagnostic errors.

Modified super-long down-regulation protocol improves fertilization and pregnancy in patients with poor ovarian responses.

BACKGROUND: The successful end-point of in vitro fertilization (IVF) treatment is for a woman to give live birth. This outcome is based on various factors including adequate number of retrieved eggs. Failure to recruit adequate follicles, from which the eggs are retrieved, is called a "poor response". How to improve the clinical pregnancy rates of poor responders was one of the tough problems for IVF. METHODS: The study involved 51 patients who responded poorly to high dose gonadotropin treatment in their previous cycles at our reproductive center, between April 2010 and February 2012. The previous cycle (group A) received routine long protocol; the subsequent cycle (group B) received modified super-long down-regulation protocol. The primary outcome of the study was the number of oocytes fertilized. The increase in the pregnancy rate was the secondary outcome. Differences between the groups were assessed by using Student's t test and c(2) test where appropriate. RESULTS: The patients' average age was (36.64 ± 3.85) years. The mean duration of ovarian stimulation cycles of the group A patients was longer than those of the group B patients. The total dose of follicle-stimulating hormone (FSH) was significantly lower in the subsequent cycle. The peak value of serum estradiol on human chorionic gonadotrophin (hCG) day was lower in group A as compared with group B. The number of metaphase II oocytes recovered was significantly higher in group B. The cleavage rate in group A was significantly lower than in group B, 49 patients in group B reached embryo transfer stage, while 46 patients in group A reached this stage. Patients in group B received significantly more embryos per transfer as compared with group A. More pregnancies and more clinical pregnancies with fetal heart activity were achieved in group B. CONCLUSIONS: This comparative trial shows that poor responder women undergoing repeated assisted reproduction treatment using modified super-long down-regulation protocol achieve more oocytes, leading to higher fertilization rate, compared to women receiving routine long protocol. Our study also showed that clinical pregnancy rate was significantly improved.

[Clinicalpathological characteristics of Lynch syndrome related epithelial ovarian cancer].

OBJECTIVE: To explore the clinical pathological characteristics of Lynch syndrome associated ovarian cancer. METHODS: Totally 260 cases ovarian cancer patients were admitted to Tianjin Medical University General Hospital during Jan. 2004 and Jan. 2011, among which 10 patients (LS group) belonged to Lynch syndrome associated ovarian cancer according to Amsterdam II criteria. One hundred ovarian cancer patients without any family cancer history were enrolled randomizely as control group (sporadic group). RESULTS: Lynch syndrome associated ovarian cancer accounted for 3.8% (10/260), the incidence rate of ovarian cancer for female family members of Lynch syndrome was 8.7% (10/115). Mean age at time of diagnosis in LS group was (46 ± 7) years, significantly earlier than that in sporadic group [(56 ± 11) years, P < 0.05]. There was no statistical difference between two groups in histological type or International Federation of Gynecology and Obstetrics (FIGO) stage (P > 0.05). Most of the tissue differentiation in LS group were well or moderate differentiated, there was statistical difference between the two groups (9/10 vs. 55%, P < 0.05). The 3-year and 5-year survival rate in LS group were 87.5% and 52.5% respectively, compared with 55.4%and 22.7% in sporadic group (all P < 0.05). CONCLUSION: Compared with sporadic ovarian cancer, Lynch syndrome associated ovarian cancer is more likely present as the clinical pathological characteristics of early age of onset, serous adenocarcinoma, lower grade and better prognosis.

[Activation and significance of the PI3K/Akt pathway in endometrium with polycystic ovary syndrome patients].

OBJECTIVE: To investigate activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in the endometrium of women with polycystic ovary syndrome (PCOS) and its role in endometrium hyperplasia and carcinogenesis, and the factors affecting the activation of the PI3K/Akt pathway. METHODS: From Jan 2007 to Jun 2008, 52 patients with PCOS who underwent dilatation and curettage were selected as experimental group matched with 32 non-PCOS patients as control group. Serous hormonal parameters, fasting blood glucose and insulin, body mass index (BMI), and endometrium pathology were measured and evaluated in all patients. The PCOS patients were divided into insulin resistance and non-insulin resistance group according to homeostasis model assessment-insulin resistance index (HOMA-IR). Meanwhile, the PCOS patients were grouped as normal, endometrial hyperplasia and carcinoma depending on outcome of pathology. The expression of Akt and phosphorylated Akt (p-Akt) were determined by western blot. RESULTS: (1) The expression of p-Akt was significantly higher in PCOS group [(46 ± 18)%] than that in control [(33 ± 9)%, P < 0.01)]. (2) The expression of p-Akt was significantly higher in group of endometrial hyperplasia and carcinoma [(56 ± 19)%] when compared with those in normal endometria group [(31 ± 12)%, P < 0.05]; the expression of p-Akt was significantly higher in group of insulin resistance [(50 ± 19)%] compared with that in non-insulin resistance group [(34 ± 10)%, P < 0.01]. (3) There was a positive correlation between the expression level of p-Akt in endometrium with PCOS and HOMA-IR and BMI respectively (r = 0.400, 0.326, both P < 0.05). CONCLUSIONS: The PI3K/Akt pathway was over activated in endometrium with PCOS which may be associated with the formation of endometrial hyperplasia and carcinoma in PCOS patients. Insulin resistance and obesity may be high risk factors for over-activation of the PI3K/Akt pathway in endometrium with PCOS.

[Analysis of human papillomavirus type 61, 83 and 84 MY fragments and preparation of standard samples].

OBJECTIVE: To investigate the mutations in nucleotide and amino acid level in HPV61, 83 and 84 Shanxi isolates. METHODS: Amplified fragments of HPV61, 83 and 84 from human papillomavirus (Human papillomavirus, HPV) molecular epidemiologic survey of Shanxi Province using HPV consensus primers MY09/11 were cloned in pMD18-T vector, and the plasmids were sequenced, then nucleotide sequences and amino acid sequences were analyzed. RESULTS: HPV61 and HPV83 isolates were consistent with reference strains U31793 and AF151983 in nucleotide sequences; four mutations of nucleotide (C6760T, T6931C, T6951C and C6987A) were found in HPV84 isolate compared with reference strain AF293960, among which C6987A resulted in D441E and the amplified sensitivity of standard sample of HPV61 using primers MY09/11 was higher than that of HPV83 and 84. CONCLUSION: HPV61 and HPV83 isolates were consistent with reference strains, four mutations of nucleotide and one mutation of amino acid were found in HPV84,the amplified sensitivity of standard sample of HPV61 using primers MY09/11 was the highest among those three isolates.

[Clinical characteristics of aerobic vaginitis and its mixed infections].

OBJECTIVE: To investigate clinical characteristics of aerobic vaginitis (AV) and its mixed infections for diagnosis efficiently. METHODS: From April 2008 to December 2008, 516 patients with vaginitis treated in Tianjin Medical University General Hospital were enrolled in this study. AV, bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), trichomonal vaginitis (TV), and cytolytic vaginosis (CV) were diagnosed based on symptoms, sign and vaginal discharge examination. RESULTS: Among 516 cases, AV cases were found in 14.7% (76/516), and AV was common vaginal infection. AV mixed infections was diagnosed in 58% (44/76), including mixed with BV (45%, 20/44), mixed with VVC (30%, 13/44), and mixed with TV (25%, 11/44). Those common symptom of AV were yellow vaginal discharge (63%, 20/32), more vaginal discharge (44%, 14/32). Vaginal pH value was usually more than 4.5 (84%, 27/32). Vaginal cleanliness mainly was grade III - IV (88%, 28/32). Six cases with enterococcus faecium and 4 cases with streptococci were frequently isolated. The symptom and sign of mixed AV infection was atypical. CONCLUSIONS: Aerobic vaginitis is a common lower vaginal infection and easily mixed with other pathogens, especially with BV, VVC or TV. When patients were diagnosed with AV or other vaginal infection, it should be mentioned whether those patients have mixed vaginal infection or AV.