Key clinical predictors in the diagnosis of ovarian torsion in children

Abstract Objective: Ovarian torsion (OT) represents a severe gynecological emergency in female pediatric patients, necessitating immediate surgical intervention to prevent ovarian ischemia and preserve fertility. Prompt diagnosis is, therefore, paramount. This retrospective study set out to assess the utility of combined clinical, ultrasound, and laboratory features in diagnosing OT. Methods: The authors included 326 female pediatric patients aged under 14 years who underwent surgical confirmation of OT over a five-year period. Logistic regression analysis was employed to pinpoint factors linked with OT, and the authors compared clinical presentation, laboratory results, and ultrasound characteristics between patients with OT (OT group) and without OT (N-OT group). The authors conducted receiver operating characteristic (ROC) curve analysis to gauge the predictive capacity of the combined features. Results: Among 326, OTwas confirmed in 24.23 % (79 cases) of the patients. The OT group had a higher incidence of prenatal ovarian masses than the N-OT (22 cases versus 7 cases) (p < 0.0001). Similarly, the authors observed significant differences in the presence of lower abdominal pain, suspected torsion on transabdominal ultrasound, and a high neutrophil-lymphocyte ratio (NLR > 3) between the OTand non-OT groups (p < 0.05). Furthermore, when these parameters were combined, the resulting area under the curve (AUC) was 0.868, demonstrating their potential utility in OT diagnosis. Conclusion: This study demonstrates a prediction model integrating clinical, laboratory, and ultrasound findings that can support the preoperative diagnosis of ovarian torsion, thereby enhancing diagnostic precision and improving patient management. Future prospective studies should concentrate on developing clinical predictive models for OTin pediatric patients.

Tumores en ovario en pediatría / Ovarian tumors in pediatrics

Los tumores de ovario en la edad pediátrica son raros, representan 1-5 % de los tumores infantiles, con una incidencia anual de 2,6 casos por cada 100.000 pacientes. La mayoría son benignos y se tratan de quistes funcionales, sin embargo, entre 10-20 % son malignos y generalmente se presentan en adolescentes; estos últimos, se dividen en 3 grupos: tumores epiteliales, germinales, y estromales o de células sexuales. Método: Estudio retrospectivo de tipo transversal, observacional, no experimental. Se analizaron los pacientes con diagnóstico de tumor de ovario, ingresados en el Servicio de Cirugía Pediátrica del Hospital de Niños "Dr. José Manuel de los Ríos", entre el 1 de enero de 2017 y 01 de julio de 2022. Resultados: 18 pacientes incluidos en el estudio, con edad media de 8,23 años (DE 4,77); los síntomas más frecuentes presentados al momento del ingreso fueron: aumento de volumen abdominal (52,94 %, 9 pacientes), y dolor abdominal (35,29 %, 6 pacientes), entre otros. Reporte patológico: 2 pacientes con quistes de ovario funcional (11,76 %) y 16 pacientes con tumor neoplásico (88,23 %), de los cuales 8 fueron germinales (53,33 %), 5 tumores epiteliales (33,33 %) y 2 pacientes con linfoma (13,33 %). Conclusión: Los tumores de ovario en general tienen una edad promedio de presentación de 8 años y los tumores neoplásicos se presentaron principalmente en adolescentes, siendo el tipo histológico más frecuente el tumor germinal y dentro de este grupo el teratoma quístico maduro. (AU)

Ovarian tumors in pediatric age are rare, representing 1-5 % of childhood tumors, with an annual incidence of 2.6 cases per 100,000 patients. Most of them are benign and functional cysts; however, between 10-20 % are malignant and generally occur in teenagers; the latter are divided into 3 groups: epithelial, germinal, and stromal or sex cell tumors. Methods: Retrospective, cross-sectional, observational, non-experimental study. Patients with a diagnosis of ovarian tumor, admitted to the Pediatric Surgery Service of the Children's Hospital "Dr. José Manuel de los Ríos", between January 01, 2017 and July 01, 2022, were analyzed. Results: 18 patients included in the study, with mean age 8.23 years (SD 4.77); the most frequent symptoms presented at admission were: increased abdominal volume (52.94 %, 9 patients), and abdominal pain (35.29 %, 6 patients), among others. Pathological report: 2 patients with functional ovarian cysts (11.76 %) and 16 patients with neoplastic tumor (88.23 %), of which 8 were germinal (53.33 %), 5 epithelial tumors (33.33 %) and 2 patients with lymphoma (13.33 %). Conclusion: Ovarian tumors in general have an average age of presentation of 8 years and neoplastic tumors occurred mainly in teenagers, the most common histological type being the germ cell tumor and within this group the mature cystic teratoma. (AU)

Uso de ileostomía derivativa en cáncer de ovario. Revisión de la literatura / Use of diverting ileostomy in ovarian cancer. Literature review

Introducción. La ileostomía derivativa de protección se realiza con el objetivo de proteger la anastomosis intestinal después de una resección colorrectal. Esta resección intestinal es el procedimiento extendido más frecuentemente realizado en pacientes con cáncer de ovario, con el fin de lograr una citorreducción completa. Conocer las indicaciones, el uso, las técnicas y las complicaciones de las ileostomías es importante para los grupos multidisciplinarios que tratan estas pacientes. Métodos. Se realizó una búsqueda en PubMed vía Medline y una revisión narrativa actualizada de los principales hallazgos sobre las indicaciones, las técnicas quirúrgicas, complicaciones y el uso de la ileostomía derivativa en el cáncer de ovario. Resultados. El uso de la ileostomía derivativa en cáncer de ovario sigue siendo un tema controvertido. Hasta la fecha, ni la ileostomía de derivación ni la ileostomía fantasma se han asociado con una reducción en la incidencia de la fuga anastomótica, pero ambas técnicas podrían disminuir su gravedad. Conclusión. La ileostomía de derivación en cáncer de ovario se usa para proteger una anastomosis distal tras una resección intestinal, en caso de fuga anastomótica si no se ha realizado una ostomía previa o en caso de obstrucción intestinal.

Introduction. Protective diverting ileostomy is performed with the aim of protecting the intestinal anastomosis after a colorectal resection. This intestinal resection is the most frequently performed extended procedure in patients with ovarian cancer, in order to achieve complete cytoreduction. Knowing the indications, use, techniques and complications of ileostomies is important for multidisciplinary groups that treat these patients. Methods. We conducted a search in PubMed via Medline and an updated narrative review of the main findings on the indications, surgical techniques, complications and use of diverting ileostomy in ovarian cancer. Results. The use of diverting ileostomy in ovarian cancer remains a controversial issue. To date, neither diverting ileostomy nor ghost ileostomy have been associated with a reduction in the incidence of anastomotic leak, but both techniques could decrease its severity. Conclusion. The diverting ileostomy in ovarian cancer is used to protect a distal anastomosis after intestinal resection, in case of anastomotic leak if a previous ostomy has not been performed or in case of intestinal obstruction.

Fibroma bilateral de ovario en mujer posmenopáusica. Reporte de un caso y revisión de la literatura / Bilateral ovarian fibroma in postmenopausal woman. Case report and literature review

Los fibromas ováricos son tumores benignos poco frecuentes, generalmente unilaterales, que se presentan principalmente en mujeres perimenopáusicas y posmenopáusicas. Los síntomas pueden variar y en algunos casos están asociados a ascitis y derrame pleural, conocido como síndrome de Meigs. Se presenta un caso de una paciente de 55 años de edad con antecedentes de hipertensión arterial y asma bronquial, quién acude a ginecólogo por dolor en fosa ilíaca derecha de tres meses de evolución. Se realizan diferentes estudios incluyendo ecografía y tomografía abdomino-pélvica, los cuales revelan una tumoración sólida bilateral de ovarios. Se realiza histerectomía abdominal total más salpingo-oforectomía bilateral y a pesar de sus características, el estudio histopatológico hace el diagnóstico de fibroma bilateral. La presentación clínica de los fibromas de ovario es inespecífica, por lo que suelen confundirse con patología maligna del ovario u otras patologías benignas de útero u ovario, constituyendo un reto para el diagnóstico preoperatorio(AU)

Ovarian fibromas are rare tumors that mainly occur in perimenopausal and postmenopausal women. Symptoms can vary, and in some cases, they may be associated with ascites and pleural effusion, known as Meigs Syndrome. The article presents the case of a 55-year-old patient with a history of hypertension and bronchial asthma, who visit a gynecologist due to pain in the right iliac fossa of three months duration. Various studies were performed, including ultrasound and abdominal and pelvic CT, which reveal the presence of solid bilateral ovarian tumors. The patient undergoes a total hysterectomy and bilateral salpingo-oophorectomy and despite it's characteristics, the histopathological study makes the diagnosis of bilateral ovarian fibroma with no signs of malignancy. The clinical presentation of ovarian fibromas is nonspecific, often leading to confusion with malignant ovarian pathology or other benign uterine or ovarian conditions, representing a challenge for preoperative diagnosis(AU)

Tumor de los cordones sexuales con estructuras túbulo anulares. Presentación de un caso no asociado a síndrome de Peutz-Jeghers

El tumor de los cordones sexuales con estructuras túbulo anulares (TCSTA) es un tumor ovárico extremadamente infrecuente representando el 1%-2% de los tumores de los cordones sexuales. Cuando existe asociación con síndrome de Peutz-Jeghers (SPJ) el tumor generalmente tiene un comportamiento benigno, no así en la ausencia de esta asociación. Se presenta el caso de una paciente de 18 años con sus características clínicas e histopatológicas.

Sex cord tumor with tubule-annular structures (TCSTA) is a rare ovarian tumor, representing 1%-2% of sex-cord stromal tumors. When there is an association with Peutz-Jeghers syndrome (SPJ), the tumor generally behaves benignly, but not without this association. The case of an 18-year-old patient with its clinical and histopathological characteristics is presented.

PITPNA-AS1 Inhibits Cell Proliferation and Migration in Ovarian Cancer by Regulating the MIR-223-3p/RHOB Axis

ABSTRACT Background: Ovarian cancer is a fatal gynecologic malignancy. Long non-coding RNA (lncRNA) has been verified to serve as key regulator in ovarian cancer tumorigenesis. Objective: The aim of the study was to study the functions and mechanism of lncRNA PITPNA-AS1 in ovarian cancer cellular process. Methods: Clinical ovarian cancer samples were collected and stored at an academic medical center. Cellular fractionation assays and fluorescence in situ hybridization were conducted to locate PITPNA-AS1 in OC cells. TUNEL staining, colony-forming assays, and Transwell assays were performed for evaluating cell apoptosis as well as proliferative and migratory abilities. Western blot was conducted for quantifying protein levels of epithelial-mesenchymal transition markers. The binding relation between genes was verified by RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. Gene expression levels in ovarian cancer tissues and cells were subjected to RT-qPCR. Results: PITPNA-AS1 level was downregulated in ovarian cancer samples and cells. PITPNA-AS1 overexpression contributed to the accelerated ovarian cancer cell apoptosis and inhibited cell migration, proliferation, and epithelial-mesenchymal transition process. In addition, PITPNA-AS1 interacted with miR-223-3p to regulate RHOB. RHOB knockdown partially counteracted the repressive impact of PITPNA-AS1 on ovarian cancer cell activities. Conclusion: PITPNA-AS1 inhibited ovarian cancer cellular behaviors by targeting miR-223-3p and regulating RHOB. (Rev Invest Clin. 2024;76(2):103-15)

Hiperandrogenismo por tumor ovárico de células esteroideas en paciente pediátrico / Hyperandrogenism due to ovarian steroid cell tumor in a pediatric patient

RESUMEN Los tumores de ovario son raros en pediatría. En este grupo, los tumores de células esteroideas representan el 0,1% de los casos y existen escasos reportes en la literatura. Presentamos el caso de una niña de 11 años con síntomas de engrosamiento de la voz, hirsutismo, acné y clitoromegalia. El análisis de laboratorio mostró niveles elevados de testosterona total y libre, niveles normales de 17-hidroxiprogesterona. La evaluación ecográfica reveló un agrandamiento significativo del ovario izquierdo. La paciente fue sometida a salpingooforectomía izquierda. Este hallazgo fue consistente con un tumor de células esteroideas de ovario. A esto le siguió la reducción gradual de los andrógenos y la mejoría clínica. Los tumores de células esteroideas son raros en pediatría, sin embargo, deben considerarse como diagnóstico diferencial al estudiar pacientes con síntomas de hiperandrogenismo.

ABSTRACT Ovarian tumors are rare in pediatrics. In this group, steroid cell tumors represent 0.1% of total cases and there are few reports in the literature. We present the case of an 11-year-old girl who suffered from deeper voice, hirsutism, acne and clitoromegaly. Analysis showed elevated levels of total and free testosterone, normal levels of 17-hydroxyprogesterone. Ultrasound evaluation revealed significant enlargement of the left ovary. The patient underwent left salpingo-oophorectomy. This finding is consistent with an ovarian steroid cell tumor. This is followed by gradual reduction of androgens and clinical improvement. Steroid cell tumors are rare in pediatrics, however, they should be considered as a differential diagnosis when studying patients with symptoms of hyperandrogenism.

Cistoadenoma mucinoso gigante de ovario / Giant ovarian mucinous cystadenoma

Aunque el cistoadenoma mucinoso de ovario tiene un crecimiento benigno, puede crecer hasta tener grandes dimensiones. Se presenta el caso de una paciente de 70 años que acudió a consulta por presentar dolor abdominal recurrente y difuso. A la exploración física se palpó una gran masa que ocupaba toda la cavidad abdominal, hasta la apófisis xifoides, redondeada, renitente, de bordes definidos, no dolorosa, no movible. Presencia de edema en miembros inferiores. Durante el acto operatorio se identificó útero miomatoso y quiste gigante de ovario izquierdo, aproximadamente de 40 x 30 cm y 13,6 kg de peso. Se realizó histerectomía total abdominal y salpingooforectomía bilateral. La biopsia confirmó el diagnóstico de cistoadenoma mucinoso benigno de ovario y leiomiomatosis uterina. El posoperatorio transcurrió favorablemente. La incidencia de cistoadenoma gigante de ovario es desconocida, debido a la falta de un concepto estandarizado y las modalidades de imagen avanzadas disponibles en la actualidad(AU)

Although ovarian mucinous cystadenoma has a benign growth, it can grow to be very large. We present the case of a 70-year-old patient who came to the clinic for recurrent and diffuse abdominal pain. On physical examination, a large mass was palpated that occupied the entire abdominal cavity, up to the xiphoid appendix, rounded, retentive, with defined edges, non- painful, non-movable. Presence of edema in lower limbs. During the surgical act, a myomatous uterus and a giant left ovarian cyst measuring approximately 40 x3 0 cm and weighing 13.6 kg were identified. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The biopsy confirmed the diagnosis of benign ovarian mucinous cystadenoma and uterine leiomyomatosis. The postoperative period progressed favorably. The incidence of giant ovarian cystadenoma is relatively unknown due to the lack of a standardized concept and currently available advanced imaging modalities(AU)

Tumor de células de la granulosa tipo juvenil tras la menopausia / Juvenile granulosa cell tumor in menopausal woman

Los tumores de células de la granulosa son tumoraciones ováricas infrecuentes. Hay dos tipos histológicos: adulto y juvenil. Los tumores de células de la granulosa juvenil representan el 5 %, y solamente un 3 % ocurre en mayores de 30 años. Ante la sospecha, el diagnóstico definitivo intraoperatorio es complejo dada su rareza y su fácil confusión con otras neoplasias ováricas. El patrón quístico con células de la granulosa inmaduras, con frecuentes mitosis, la ausencia de cuerpos de Call-Exner y el estudio inmunoquístico lo confirman. Su baja prevalencia dificulta su diagnóstico. El estadio de la enfermedad es el factor pronóstico más importante, y resulta imprescindible una completa resección. El papel de la terapia complementaria no está bien establecido, además los estudios disponibles solamente incluyen un número mínimo de casos, que no diferencian mujeres adultas. El adecuado seguimiento para la detección precoz de una posible recidiva tardía supone un reto clínico(AU)

Granulosa cell tumors are rare ovarian tumors. There are two histological types: adult and juvenile. Juvenile granulosa cell tumors account for 5%, with only 3% occurring in people over 30 years of age. Given the suspicion, the definitive intraoperative diagnosis is complex given its rarity and its easy confusion with other ovarian neoplasms. The cystic pattern with immature granulosa cells, with frequent mitosis, the absence of Call-Exner bodies and the immunocystic study confirm this. Its low prevalence makes it difficult to diagnose. The stage of the disease is the most important prognostic factor, and complete resection is essential. The role of complementary therapy is not well established, and the available studies include only a minimal number of cases, which do not differentiate between adult women. Adequate follow-up for the early detection of a possible late recurrence is a clinical challenge(AU)

Trichostatin A-modified vaccine provides superior protection against ovarian cancer formation and development

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.

Características clínicas en pacientes con menos de 12 folículos ováricos como hallazgo ecográfico / Clinical and ultrasound findings in patients with ovaries with a count of less than 12 follicles

Introducción y objetivos: Determinar los hallazgos clínicos y ecográficos en pacientes que presentan menos de 12 folículos ováricos. Método: Estudio observacional (cohorte histórica) con 505 pacientes seleccionadas mediante muestreo consecutivo, entre el 14 de enero del 2019 y el 15 de marzo del 2021, que consultan por diversas alteraciones ginecológicas. Se generan dos grupos de pacientes, las que presentaron uno a tres folículos en uno de los ovarios (n = 377) y las que presentaban 4 a 11 folículos (n = 128). Se midió como resultado primario la presencia de al menos un signo clínico de hiperandrogenismo. Resultados: De 505 pacientes analizadas, al comparar las que presentaron 4 a 11 folículos en uno de los ovarios (n = 377) con las que presentaban 1 a 3 folículos (n = 128), las primeras mostraron mayor presencia de signos de hiperandrogenismo, endometrio en fase lútea de mayor espesor y un patrón menstrual con uno a cuatro días de sangrado menstrual abundante, diferencias todas estadísticamente significativas (p < 0,05). Conclusión: En pacientes con 4 a 11 folículos en uno de sus ovarios, se observaron signos de hiperandrogenismo, similares al síndrome de ovario poliquístico.

Introduction and objectives: Determine the clinical and ultrasound findings in patients who present less than 12 ovarian follicles in the ultrasound count. Method: Observational study (historical cohort) with 505 patients selected by consecutive sampling, between January 14, 2019 and March 15, 2021, who consulted for different gynecological disorders. Two groups of patients were generated: those with 1 to 3 follicles in one of the ovaries (n = 377) and those with 4 to 11 follicles (n = 128). The primary outcome was the presence of at least one clinical sign of hyperandrogenism. Results: Of 505 patients analyzed, when comparing those who presented 4 to 11 follicles in one of the ovaries (n = 377) with those who presented 1 to 3 follicles (n = 128), the first group showed a greater presence of signs of hyperandrogenism, thicker endometrium in luteal phase and a menstrual pattern with one to four days of heavy menstrual bleeding, all differences were statistically significant (p < 0.05). Conclusion: In patients with 4 to 11 follicles in one of their ovaries, signs of hyperandrogenism, similar to polycystic ovary syndrome, were observed.

Borderline ovarian tumors: a review of its biology, molecular profile, and management / Tumores borderline de ovário: uma revisão de sua biologia, perfil molecular e manejo

Borderline ovarian tumors typically exhibit indolent behavior and boast a favorable prognosis; however, a subset of patients experiences disease recurrence and progression to low-grade ovarian carcinoma. The complex biology underlying these phenomena has been illuminated through molecular analyses. KRAS and BRAF mutations have emerged as recurrent ?ndings in borderline ovarian tumors. Speci?cally, KRAS mutations have been linked to a higher risk of recurrence and progression to low-grade ovarian carcinoma, while BRAF mutations seem to confer a protective e?ect, inducing a senescent state that mitigates the likelihood of progression. In this comprehensive review, we explore the biology and the molecular pro?le of borderline ovarian tumors, shedding light on recent discoveries that have enriched our comprehension. Additionally, we discuss the current state of borderline ovarian tumors management. Surgery remains the cornerstone of treatment. While cytotoxic therapies role is limited so far, molecular characterization emphasizes the imminent potential for personalized therapeutic approaches.

Os tumores borderline de ovário geralmente exibem comportamento indolente e apresentam prognóstico favorável; no entanto, um subconjunto de pacientes apresenta recorrência da doença e progressão para carcinoma de ovário de baixo grau. A biologia complexa subjacente a estes fenômenos foi iluminada através de análises moleculares. Mutações KRAS e BRAF surgiram como achados recorrentes em tumores borderline de ovário. Especificamente, as mutações KRAS têm sido associadas a um maior risco de recorrência e progressão para carcinoma de ovário de baixo grau, enquanto as mutações BRAF parecem conferir um efeito protetor, induzindo um estado senescente que mitiga a probabilidade de progressão. Nesta revisão abrangente, exploramos a biologia e o perfil molecular dos tumores borderline de ovário, lançando luz sobre descobertas recentes que enriqueceram nossa compreensão. Além disso, discutimos o estado atual do manejo de tumores borderline de ovário. A cirurgia continua sendo o pilar de tratamento. Embora o papel das terapias citotóxicas seja limitado até o momento, a caracterização molecular enfatiza o potencial iminente para abordagens terapêuticas personalizadas.

Mechanism of Cuscutae Semen to Control Premature Ovarian Failure Based on Lipid and Atherosclerosis Pathways / 中国实验方剂学杂志

ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg-1·d-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg-1·d-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E2）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E2， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.

Clinical observation of letrozole combined with methylprednisolone in the treatment of infertile patients with polycystic ovary syndrome resistant to clomiphene / 中国药房

OBJECTIVE To explore the effects of letrozole combined with methylprednisolone on clinical outcomes， ovarian reserve function， serum sex hormones， and safety in infertile patients with polycystic ovary syndrome resistant to clomiphene. METHODS The clinical data of 78 infertile patients with polycystic ovary syndrome resistant to clomiphene in the Department of Gynecology of Qingdao Central Hospital from February 2021 to January 2022 was analyzed retrospectively， and all patients were divided into control group （42 cases） and observation group （36 cases） based on the treatment methods. The control group took letrozole 5 mg/d orally on the 5th to 9th day of the menstrual cycle. Vaginal ultrasound was used to monitor the development of the endometrium and follicles； estradiol valerate was used to correct endometrial thickness， and measures such as inducing ovulation with follicle-stimulating hormone were taken to promote pregnancy. On the basis of treatment in the control group， the observation group began taking methylprednisolone orally at a dose of 4 mg/d starting from the third day of natural menstruation or withdrawal bleeding. Both groups were treated for 6 menstrual cycles. The ovulation and pregnancy within one year， serum levels of sex hormones [estradiol （E2）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， testosterone] and anti-Müllerian hormone （AMH）， ovulation indicators （follicle growth time， the number of ovulations， and the number of dominant follicles）， and the occurrence of adverse drug reactions were compared between the two groups. RESULTS After treatment， the biochemical pregnancy rate （72.22%） and clinical pregnancy rate （47.22%） of the observation group were significantly higher than those of control group （47.62%， 19.05%）； the serum levels of E2， LH， FSH， testosterone and AMH were significantly lower than the control group； the follicle growth time was significantly shorter than the control group； the number of ovulation and dominant follicles were significantly higher than the control group （P＜0.05）. There was no statistically significant difference in ovulation rate （94.44% vs. 83.33%） and total incidence of adverse drug reactions （8.33% vs. 9.52%） between the observation group and the control group （P＞0.05）. CONCLUSIONS Compared with letrozole alone， the combination of letrozole and methylprednisolone can significantly improve the pregnancy rate， the sex hormone levels and ovarian reserve function in infertile patients with polycystic ovary syndrome resistant to clomiphene， with high safety profiles.

The correlation between YAP nuclear expression and tumor size with prognosis of epithelial ovarian cancer / 安徽医科大学学报

Objective To investigate the correlation between Yes-associated protein(YAP)nuclear expression and tumor size with prognosis of patients with epithelial ovarian cancer(EOC)and to study the role of YAP in EOC.Methods 120 patients with EOC were selected as the experimental group,including 38 patients with early stage(Ⅰ+Ⅱ)EOC and 8 2 patients with advanced stage(Ⅲ+Ⅳ)EOC.3 0 normal ovarian tissues obtained from patients with uterine leiomyoma were enrolled as the control group.Immunohistochemical(IHC)assay was em-ployed to determine YAP expression and sub-location.The relationship between YAP expression and the pathologi-cal parameters of the 120 patients with EOC was analyzed,so as to the prognosis of these patients.EOC cells(C13K and OV2008)were cultured with varying initial cell volumes.Ki67 expression and cell proliferation were tested by immunofluorescence and cloning assay respectively.YAP expression at mRNA and protein levels were de-tected by q-PCR and Western blot respectively when the cell conference of EOC cells reached to low(60％)and high(90％)cell density.Results The YAP nuclear expression was significantly higher in the EOC group com-pared to the control group(P＜0.05).The average diameter of stage Ⅰ+Ⅱ EOC was larger than that of stage Ⅲ+Ⅳ EOC(P＜0.01).The high nuclear expression of YAP was positively associated with pathological grade,clinical stage and the level of Ca125＞1 000 IU/ml,while negatively correlated with tumor size(all P＜0.05).Survival analyses showed that smaller tumor size(＜10 cm)and higher YAP nuclear expression were negatively as-sociated with the 3-year overall survival rate of EOC patients(P＜0.01).C13K and OV2008 cells cultured in the low density group exhibited a high number of clone formation,high Ki67 and YAP expression(P＜0.01).The down-regulation of YAP expression could decrease the cell viability of EOC cells in the low-and high-density groups(P＜0.05).Conclusion Higher level of YAP nuclear expression and smaller tumour size are inversely associated with the clinical prognosis of patients with EOC.Inhibiting YAP nuclear expression leads to a decrease in the prolif-eration capacity of EOC cells.

Effect of chelerythrine on migration,invasion,and epithelial-mesenchymal transition of human ovarian cancer SKOV3 cells / 吉林大学学报(医学版)

Objective:To discuss the inhibitory effect of chelerythrine(CHE)on the migration,invasion,and epithelial-mesenchymal transition(EMT)of the human ovarian cancer SKOV3 cells,and to clarify the associated mechanism.Methods:The SKOV3 cells were cultured in vitro and divided into control group and 2.5,5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups.Methylthiazolydiphenyl-tetrazolium(MTT)assay was used to detect the inhibitory rates of proliferation of the cells in various groups.The SKOV3 cells were cultured in vitro and divided into control group,transforming growth factor-β1(TGF-β1)group,TGF-β1+5 μmol·L-1 CHE group,and TGF-β1+10 μmol·L-1 CHE group.Cell scratch assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;Western blotting method was used to detect the expression levels of E-cadherin,N-cadherin,and Vimentin proteins in the cells in various groups;immunofluorescence staining method was used to detect the fluorescence intensities of E-cadherin and N-cadherin in the cells in various groups.Results:The MTT assay results showed that compared with control group,the inhibitory rates of proliferation of the cells in 5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups were significantly increased(P<0.05 or P<0.01).The cell scratch assay results showed that compared with control group,the migration rate of the cells in TGF-β1 group was increased(P<0.01);compared with TGF-β1 group,the migration rates of the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion cells in TGF-β1 group were significantly increased(P<0.05);compared with TGF-β1 group,the numbers of migration and invasion cells in TGF-β1+5 μmo·l L-1 CHE group and TGF-β1+10 μmo·l L-1 CHE group were significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in TGF-β1 group was significantly decreased(P<0.01),while the expression levels of N-cadherin and Vimentin proteins were increased(P<0.05 or P<0.01);compared with TGF-β1 group,the expression levels of E-cadherin protein in the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of E-cadherin in the cells in TGF-β1 group was decreased,and the fluorescence intensity of N-cadherin was increased;compared with TGF-β1 group,the fluorescence intensities of E-cadherin in the cells in TGF-β 1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased,and the fluorescence intensities of N-cadherin were decreased.Conclusion:CHE can inhibit the proliferation,migration,invasion,and EMT of the human ovarian cancer SKOV3 cells.

Analysis on correlation between PDK 1 and Ki-67 expression levels with survival and prognosis of patients with ovarian serous carcinoma / 重庆医学

Objective To analyze the relationship between the expression levels of pyruvate dehydro-genase kinase 1(PDK 1)and Ki-67 with the survival and prognosis of the patients with ovarian serous carci-noma(OSC).Methods The cancer tissues of 93 patients with OSC treated by surgery in this hospital from January 2000 to June 2020 were collected,and the expression levels of PDK1 and Ki-67 in the tissues were de-tected by immunohistochemistry.The relationship between the expression levels of PDK1 and Ki-67 with the clinicopathological characteristics of the patients with OSC was analyzed by the single factor and binary logis-tic regression model.The relationship between the PDK1 and Ki-67 expression levels with the recurrence and platinum resistance within 3 years was analyzed.The Kaplan-Meier survival curve was adopted to analyze the effect of PDKI and Ki-67 expression levels on the survival and prognosis in the patients with OSC.Results The expression levels of PDK1 and Ki-67 were related with the International Federation of Gynecology and Obstetrics(FIGO)stage,tissue differentiation level,lymphatic metastasis,ascites formation and positive asci-tes(P＜0.05).The high expression of PDK1 was a risk factor for the late FIGO stage(Ⅲ-Ⅳ),lymphatic metastasis and ascites positive in the patients with OSC(P＜0.05);the high expression of Ki-67 was a risk factor for the late FIGO stage(Ⅲ-Ⅳ)and ascites formationin in the patients with OSC(P＜0.05).The re-currence rate and platinum resistance rate within 3 years in the patients with PDKi and Ki-67 high expressions were significantly higher than those in the patients with low expressions(P＜0.05).The progression-free survival(PFS),overall survival(OS)and 5-year survival rate in the patients with high PDK1 and Ki-67 ex-pressions were significantly lower than those in the patients with low expressions(P＜0.05).Conclusion The expression levels of PDK 1 and Ki-67 play an important role in judging the survival and prognosis of the patients with OSC.

Transcriptomic analysis and antagonist screening of cisplatin resistance in ovarian cancer / 重庆医学

Objective To investigate the transcriptome differences of ovarian cancer cells after cisplatin(DDP)resistance,and to find potential antagonists based on this screening.Methods DDP-resistant cell line A2780-DDP was constructed with A2780 cells as the research object.Through transcriptome sequencing anal-ysis,the key factors of DDP resistance were found and verified by quantitative real-time PCR(qPCR)and Western blot experiments.Through the screening of small molecule inhibitors,CCK-8 cell viability assay was used to find potential antagonists.Results A2780-DDP were successfully constructed,and it was found that there was no difference in cell proliferation after drug resistance,but the ability of cell invasion and migration was enhanced.Through transcriptome sequencing analysis,it was found that ITGB7 and Akt may be the key genes of A2780-DDP,and qPCR and Western blot showed that they were highly expressed in A2780-DDP.CCK-8 results showed that triptolide(TPL)and Olaparib had good inhibitory effects in DDP-resistant cell lines.Conclusion The ITGB7/Akt pathway plays an important role in DDP resistance,and potential DDP re-sistance antagonists such as TPL can provide new ideas for the treatment of ovarian cancer.

Advances in treatment of acute leukemia and long-term ovarian function in children and adolescents / 国际儿科学杂志

Acute leukemia（AL）is a common hematological malignancy in children and adolescents. Chemotherapy is currently the primary treatment for AL.Alternative therapies，such as hematopoietic stem cell transplantation（HSCT），targeted therapy，and immunotherapy also offer greater hope for the survival of refractory/relapsed patients. Chemotherapeutic drugs，radiotherapy，targeted drugs and immunotherapeutic drugs are well-applied clinically，meanwhile posing threats to non-target systems. The adverse effects on the reproductive system may lead to the dilemma of infertility，thus reducing the long-term quality of life. As the survival rate of AL patients keeps increasing continuously，the influence of different treatments on the gonad function needs to be clarified. With the help of targeted fertility prevention，the patient′s quality of life can be enhanced in parallel with life span. This article aims to review the impact of AL treatment on ovarian function in female children and adolescents and provide ideas for the long-term fertility protection of leukemia patients.

Clinical study on the construction of risk prediction model for postoperative recurrence of advanced epithelial ovarian cancer based on serum HE4,PLR,RLX and KPNA2 / 国际检验医学杂志

Objective To study the construction of risk prediction model for postoperative recurrence of ad-vanced epithelial ovarian cancer based on serum human epididymis protein 4(HE4),platelet count/lymphocyte count ratio(PLR),relaxin(RLX),karyopherin α2(KPNA2).Methods 124 patients with advanced epithelial o-varian cancer diagnosed and treated in Suzhou Municipal Hospital(East District)from January 2016 to January 2019 were selected as the study objects,patients with advanced epithelial ovarian cancer were divided into re-currence group and the non-recurrence group based on whether they had recurred or not.The level of HE4 was detected by electrochemical luminescence immunoassay,PLR was calculated according to the blood routine re-sults,and RLX and KPNA2 levels were detected by enzyme-related immunosorbent assay.Multivariate Logis-tic regression analysis was used to analyze the influencing factors of postoperative recurrence in patients with advanced epithelial ovarian cancer,and establish a risk prediction model for postoperative recurrence of ad-vanced epithelial ovarian cancer.Receiver operating characteristic(ROC)curve was used to evaluate the pre-dictive efficacy of the model for postoperative recurrence of advanced epithelial ovarian cancer,and Hosmer-Lemeshow test was used to analyze the fitting of recurrence risk prediction model for patients with advanced epithelial ovarian cancer.Results There was a statistically significant difference in International Federation of Gynecology and Obstetrics(FIGO)staging and serum levels of carbohydrate antigen 125,HE4,PLR,RLX and KPNA2 between the recurrence group and the non-recurrence group(P＜0.05).FIGO staging Ⅳ of cancer and elevated serum HE4,PLR,RLX and KPNA2 were risk factors for postoperative recurrence in patients with advanced epithelial ovarian cancer(P＜0.05).ROC curve analysis showed that,the area under the curve of the recurrence risk prediction model for postoperative recurrence risk of advanced epithelial ovarian cancer was 0.859,which was significantly higher than that single indicator detected by HE4,PLR,RLX and KP-NA2.Hosmer-Lemeshow test showed that the recurrence risk prediction model of advanced epithelial ovarian cancer had a good fitting(x2=7.869,P=0.437).Conclusion The risk prediction model for postoperative re-currence of advanced epithelial ovarian cancer based on serum HE4,PLR,RLX,KPNA2 and FIGO staging of cancer has high predictive value for evaluating postoperative recurrence of advanced epithelial ovarian cancer,and deserves clinical attention.