Case report: Synchronous tumors of the female reproductive tract in systemic lupus erythematosus: report of two cases and review of the literature.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems. Patients with SLE are prone to a variety of malignancies, especially neoplasms of the female reproductive tract. Synchronous tumors, considered to involve multiple sites, are rare in the female reproductive tract. There are hardly any reports of SLE with synchronous reproductive tract tumors. Case presentation: We report the occurrence of two to three reproductive tract tumors in two women with SLE. A 52-year-old woman was diagnosed with vulvar cancer and cervical cancer. Another woman, aged 67, was diagnosed with concurrent vulvar cancer, vaginal cancer, and cervical cancer and also presented with a suspected lung cancer. Conclusion: The presence of synchronous tumors of the reproductive tract in patients with SLE is uncommon and can be easily disregarded. It is crucial to highlight that SLE patients with multiple primary malignancies exhibit notable late-stage presentation at the time of diagnosis, inadequate disease-free survival, poor overall survival, rapid progression rates, and mortality. Consequently, greater awareness must be raised regarding synchronous reproductive tract tumors in patients with SLE. Regular comprehensive cancer screening and management should be implemented for individuals diagnosed with SLE.

Machine learning-based integrated identification of predictive combined diagnostic biomarkers for endometriosis.

Background: Endometriosis (EM) is a common gynecological condition in women of reproductive age, with diverse causes and a not yet fully understood pathogenesis. Traditional diagnostics rely on single diagnostic biomarkers and does not integrate a variety of different biomarkers. This study introduces multiple machine learning techniques, enhancing the accuracy of predictive models. A novel diagnostic approach that combines various biomarkers provides a new clinical perspective for improving the diagnostic efficiency of endometriosis, holding significant potential for clinical application. Methods: In this study, GSE51981 was used as a test set, and 11 machine learning algorithms (Lasso, Stepglm, glmBoost, Support Vector Machine, Ridge, Enet, plsRglm, Random Forest, LDA, XGBoost, and NaiveBayes) were employed to construct 113 predictive models for endometriosis. The optimal model was determined based on the AUC values derived from various algorithms. These genes were then evaluated using nine machine learning algorithms (Random Forest, SVM, Gradient Boosting Machine, LASSO, XGB, NNET, Generalized Linear Model, KNN, and Decision Tree) to assess significance scores and identify diagnostic genes for each algorithm. The diagnostic value of these genes was further validated in external datasets from GSE7305, GSE11691, and GSE120103. Results: Analysis of the GSE51981 dataset revealed 62 DEGs. The Stepglm [Both] and plsRglm algorithms identified 30 genes with the most potential using the AUC evaluation. Subsequently, nine machine learning algorithms were applied to select diagnostic genes, leading to the identification of five key diagnostic genes using the LASSO algorithm. The ADAT1 gene exhibited the best single-gene predictive performance, with an AUC of 0.785. A combination of genes (FOS, EPHX1, DLGAP5, PCSK5, and ADAT1) achieves an AUC of 0.836 in the test dataset. Moreover, these genes consistently exhibited an AUC exceeding 0.78 in all validation datasets, demonstrating superior predictive performance. Furthermore, correlation analysis with immune infiltration strengthened their predictive value by demonstrating the close relationship of the diagnostic genes with immune infiltrating cells. Conclusion: A combination of biomarkers consisting of FOS, EPHX1, DLGAP5, PCSK5, and ADAT1 can serve as a diagnostic tool for endometriosis, enhancing diagnostic efficiency. The association of these genes with immune infiltrating cells reveals their potential role in the pathogenesis of endometriosis, providing new insights for early detection and treatment.

Autophagy-dependent ferroptosis is involved in the development of endometriosis.

OBJECTIVE: Endometriosis (EMS) is an estrogen-dependent condition with unclear pathogenesis. Recent findings suggest implicate autophagy and ferroptosis in EMS development. METHODS: We assessed autophagy and ferroptosis proteins in EMS patients using immunohistochemistry and western blot and established an EMS rat model through allograft endometrial transplantation, confirmed via hematoxylin and eosin staining and epithelial-mesenchymal transition -related proteins. Primary EMS cells were isolated from the model rats and cultured under five conditions: control, EMS, EMS with Rapamycin (autophagy inducer), EMS with si-Atg5 (autophagy inhibitor), and EMS with si-Atg5 plus Erastin (ferroptosis inducer). We evaluated cell viability, iron content, oxidative stress, and mitochondrial morphologyin EMS cells, and detected autophagy and ferroptosis proteins through immunofluorescence, western blot, and monodansylcadaverine staining. RESULTS: Autophagy proteins Beclin1 and LC3 were highly expressed, whereas p62, glutathione peroxidase 4, and p53 were lowly expressed in EMS patients. Rapamycin decreased cell viability but increased iron content, reactive oxygen species, lipid peroxide production, the number of ferroptotic mitochondria, and the expression of autophagy proteins in EMS cells, while si-Atg5 showed opposite effects. Additionally, Erastin reversed the impact of si-Atg5 on EMS cells. CONCLUSION: Our findings suggest that autophagy-dependent ferroptosis plays a role in EMS progression.

Copious vaginal discharge finally diagnosed as cervical adenocarcinoma: A case report.

RATIONALE: Copious vaginal discharge is a frequent manifestation of reproductive tract infections. However, when little effect can obtain treated as vaginitis, cervical disease should be highly suspected. PATIENT CONCERNS: A 41-year-old woman had suffering from abnormally increased vaginal discharge without any other signs of discomfort for the past 4 years. A lot of medical examinations and treatment of vaginosis were administered, resulting in unclear diagnosis and little effect. DIAGNOSES: Cervical adenocarcinoma. INTERVENTIONS: Gynecological examination, vaginal microbiome culture, and primary cervical cancer screening were negative, and a positron emission tomography revealed an increased 18F-fluorodeoxyglucose metabolism in the local cervix. After a thorough description, the patient demanded a hysterectomy and bilateral salpingo-oophorectomy. OUTCOMES: Histopathological evaluation confirmed adenocarcinoma in situ of the uterine cervix. LESSONS: The correct diagnosis of symptomatic patients with increased vaginal discharge is challenging. Human papillomavirus-negative patients presenting profuse watery vaginal discharge with an abnormal signal of cervix lesion on positron emission tomography or magnetic resonance imaging should be alert to cervical adenocarcinoma. Deep-seated cervical biopsy, conization, or even hysterectomy is conducive to early diagnosis, treatment and improvement of prognosis.

A novel technique for moderate to severe intrauterine adhesions: A historical cohort study.

To evaluate the feasibility and efficiency of our novel technique, ultrasound guided hysteroscopic catheter dilation (US-HCD), for the treatment of moderate to severe intrauterine adhesion (IUA). A total of 126 patients diagnosed with IUA and met the enrollment criteria were admitted in this historical cohort study from June 1, 2016 to December 31, 2018. All patients were divided into 2 groups according to the surgical techniques used. Group A (n = 68) were treated with traditional hysteroscopic adhesiolysis with scissors (THA) and Group B (n = 58) were treated with US-HCD. Their data for the next 2 years following the initial surgery were analyzed. Safety and feasibility (operation time, surgical complications and the third-look hysteroscopic surgery rate), and post-operation efficacy (reduction of American Fertility Society [AFS] scores, pregnancy and live birth rates) were evaluated between groups. Between the groups, there was no statistically significant differences in basic preoperative information and AFS scores (P > .05). While there were significant differences in the operation time of the initial surgery (P < .05) and reduction of AFS scores (P < .05). No surgical complications were recorded and only 3 patients (5.2%) received a third-look hysteroscopy in Group B, while there were 6 cases of complications and 13 cases (19.1%) of third-look hysteroscopy in Group A, indicating significant differences between Groups (P < .05). Both groups exhibited comparable pregnancy rate, live birth rate and obstetric complications (P > .05). Our new technique is a safe, feasible and effective procedure for moderate to severe IUA patients, which can be mastered more quickly and easily by surgeons and applied in areas with less affluent economy and without hysteroscopic scissors, thus worthy of further study.

Effect of Neiyi Prescription of QIU on autophagy and angiogenic ability of endometriosis via the PPARγ/NF-κB signaling pathway.

OBJECTIVES: Neiyi Prescription of QIU (NYPQ) is a traditional Chinese medicine prescription for the treatment of endometriosis (EMS). Here, we aimed to examine the effects and mechanisms of NYPQ on angiogenic ability in EMS. STUDY DESIGN: EMS rats were established with estradiol valerate and autologous transplantation. EMS rats were intraperitoneally injected with chloroquine (CQ, 40 mg/kg), rapamycin (RAPA, 1 mg/kg), and monoclonal antibody VEGF (anti-VEGF, 3 mg/g/d) or administered 5, 10, 20 mg/g/d NYPQ decoction through oral gavage for 4 weeks, respectively. By the before and end of the treatment period, the volume of the endometriotic lesions was measured. The pathological morphology, angiogenesis, and the number of autophagosomes of the endometriotic lesion were observed by hematoxylin and eosin staining, immunohistochemistry, and transmission electron microscope, respectively. The cell viability, apoptosis, and angiogenesis of HUVECs were detected by MTT, flow cytometry, and lumen formation experiment, respectively. The expression levels of VEGF, autophagy-/apoptosis-/PPARγ/NF-κB- pathway-related proteins in endometrium tissues or HUVECs were detected by western blot assays. RESULTS: The autophagy agonist rapamycin reduced the lesion size, the microvessel density, and VEGF expression, and promoted the production of autophagosomes and the expression of autophagy-related proteins, while the autophagy inhibitor chloroquine had the opposite effects. In vivo, NYPQ could dose-dependently reduce lesion volume and microvessel density, ameliorate histopathological features and promote autophagosome production of ectopic endometrium. Moreover, serum-containing NYPQ could significantly inhibit the cell viability and tube formation of HUVECs and elevate HUVECs apoptosis. Besides, NYPQ significantly reduced VEGF and promoted autophagy-/apoptosis-related protein expressions. Also, NYPQ might promote autophagy and inhibit angiogenesis by activating the PPARγ/NF-κB pathway. CONCLUSIONS: Collectively, these findings indicate that NYPQ has therapeutic potential in experimentally induced peritoneal endometriosis, and its mechanism may be related to the activation of the PPARγ/NF-κB signaling pathway.

Fuzheng Jiedu Decoction Induces Apoptosis and Enhances Cisplatin Efficacy in Ovarian Cancer Cells In Vitro and In Vivo through Inhibiting the PI3K/AKT/mTOR/NF-κB Signaling Pathway.

Objectives: This study is aimed at investigating the anticancer activity of Fuzheng Jiedu decoction (FJD) alone or in combination with cisplatin in ovarian cancer (OC) models, as well as its underlying mechanisms of action. Methods: The anticancer activities of FJD, cisplatin, and the combination of the PI3K inhibitor (LY294002, LY) or activator (IGF-1) were evaluated in OC cell lines in vitro and in a SKOV3 xenograft mouse model in vivo. The cell proliferation and invasion ability were measured using MTT, EdU, and transwell assays, respectively. The cell apoptosis was examined by flow cytometry and JC-1 assays. The expression levels of the Bcl-2 family and the PI3K/AKT/mTOR/NF-κB pathway-related proteins were analyzed by Western blot. Results: The in vivo and in vitro studies showed that FJD administration could significantly inhibit cell proliferation and promote cell apoptosis in two OC cell lines SKOV3 and 3AO and partially decreased the tumor volumes and weights. In addition, FJD could significantly downregulate the protein levels of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, NF-κB, p38, and Bcl-2 and upregulate the Bax, Cyt-C, and cleaved caspase-3 in OC tumor tissues and cells. FJD cotreatment increased the efficacy of cisplatin, including inhibiting OC cell proliferation and invasion, promoting cell apoptosis, and inhibiting the PI3K/AKT/mTOR signaling pathway, while this enhancement was suppressed by IGF-1. Similarly, LY also enhanced the anticancer efficacy of cisplatin. Conclusions: This study indicated that FJD could improve the efficacy of cisplatin by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. It is suggested that FJD may be a valuable adjuvant drug for the treatment of OC.

Qiu's Neiyi Recipe Regulates the Inflammatory Action of Adenomyosis in Mice via the MAPK Signaling Pathway.

BACKGROUND: The management of adenomyosis is challenging and limiting. Qiu's Neiyi recipe (Qiu) is a traditional Chinese medicine (TCM) prescription clinically used for endometriosis treatment in China, but the effect and mechanism of Qiu on adenomyosis are undefined. METHODS: An experimental adenomyosis model was induced in female neonatal ICR mice administrated with tamoxifen. The adenomyosis mice were divided into five groups: high-, middle-, and low-Qiu's group, danazol group, and model group. The mice just administrated with the solvent only (no tamoxifen or drugs) were served as the control group. After 28 days of administration, the body, uterine, spleen, and thymus weights of all mice were examined. Then, the myometrial infiltration and the expression of inflammatory factors were detected by histology examination, ELISA, and qRT-PCR in the uterus. In addition, the MAPK/ERK signaling pathway-related protein expression in adenomyosis mice was detected by immunohistochemical (IHC) staining, qRT-PCR, and western blotting. RESULTS: In experimental adenomyosis mice, Qiu treatment improved the symptoms of adenomyosis by reducing the myometrial infiltration and increasing the index of spleen and thymus. The elevated levels of IL-1ß, IL-6, and TNF-α in serum and uterus tissues of adenomyosis model mice were also decreased after Qiu treatment. The improvement of Qiu on the adenomyosis was achieved by inhibiting the activated MAPK/ERK signaling pathway, including reducing the mRNA and protein expressions of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 in the uterus tissues. CONCLUSION: Qiu alleviated the inflammatory reaction and uterus histological changes in mice with adenomyosis, and the potential mechanism is through the inhibition of the MAPK/ERK signaling pathway. Qiu may be a promising treatment for adenomyosis.

Advanced uterine adenosarcoma with sarcomatous overgrowth in a young woman: A case report.

RATIONALE: Uterine adenosarcoma (UA) with sarcomatous overgrowth (ASSO) is a rare and aggressive disease. Herein, wereported the case of a young patient with advanced uterine ASSO. PATIENTS CONCERNS: A 29-year-old woman with the diagnoses of endometrial polyp and adenomyosis underwent hysteroscopic endometrial polypectomy for the giant endometrial polyp. Postoperative regular ultrasound scan indicated thickened endometriumand an ill-defined mass with continuous enlargement in the myometrium of the posterior wall of the uterus, which was considered as an adenomyoma. Two years after hysteroscopy, she was re-admitted due to lower abdominal distension and large pelvic mass. At that time, she had taken oral short-acting contraceptives for 2.5 years. DIAGNOSES: Magnetic resonance imaging (MRI) of the pelvis revealed an irregular mass with the size of 12*56*107 mm in the right annex area, without distinct border with the rectum, moreover, an uneven intrauterine echo that has no obvious boundary with uterine wall. Right ovarian cancer and adenomyoma were initially considered. INTERVENTIONS: The patient received transperitoneal retroperitoneal pelvic combined with total viscera resection, including uterus, bilateral appendages and rectum, omentectomy, appendectomy, lymphadenectomy, and ileostomy. Postoperative pathology confirmed ASSO in the uterine cavity and muscular layer, the whole cervical duct and the right adnexal. She underwent 2 systemic chemotherapy sessions after the surgery. The chemotherapy regimen was ifosfamide 2.5 g day 1 to 3, with liposomal doxorubicin 40 mg day 1. OUTCOMES: The final diagnosis was uterine ASSO, International Federation of Gynecology and Obstetrics stage IVa. The patient has been following-up so far, with no progression. LESSONS: Review of the case indicated that history of long-term oral short-acting contraceptives and giant endometrial polyps may be the high-risk factors for UA. For patients with high-risk factors, the follow-up ultrasound scan should be more frequently conducted. Moreover, 3D-ultrasound, MRI and outpatient hysteroscopy are recommended for routine screening. Placement of levonorgestrel-releasing intra-uterine system after hysteroscopy may be an effective intervention for patients with a high risk of giant polyps. Cluster of Differentiation 10, Estrogen receptor, Progesterone receptor, and nuclear antigen may be predictors for prognosis and selection of individualized treatment program.

Treatment of menorrhagia due to aplastic anemia by hysteroscopic resection of endometrial functional layer and levonorgestrel-releasing intra-uterine system: Three case reports.

RATIONALE: In women, menorrhagia associated with aplastic anemia (AA) is secondary to thrombocytopenia and can be acute and severe. Endometrial ablation or hysterectomy has been reported to achieve beneficial results. However, serious limitations and long-term complications exist. We report this clinical case series with the aim of sharing our experiences and exploring a safe and effective way to treat abnormal uterine bleeding (AUB) AA women with future fertility desire. PATIENT CONCERNS: The 3 young patients aged 25 to 29 years old suffered from AUB secondary to AA. DIAGNOSIS: They were diagnosed with AA by bone marrow biopsy and presented with symptoms and signs of AUB without other identified causations. INTERVENTIONS: When the platelet count was between 30*10 /L∼50*10 /L after a blood transfusion, each patient received a hysteroscopic resection of endometrial functional layer and was fitted a levonorgestrel-releasing intra-uterine system (LNG-IUS) in uterine cavity following the surgery. OUTCOMES: All the patients recovered without incident and were discharged in clinically stable conditions. LESSONS: In conclusion, AUB secondary to AA can be acute and severe. Hemostasis is more difficult due to progressive pancytopenia. For young women with future fertility desire, LNG-IUS following hysteroscopic resection of endometrial functional layer is a safe and effective way against endometrial ablation or hysterectomy.

Recurrent ovarian hemorrhage in a patient with aplastic anemia: A case report.

RATIONALE: Recurrent ovarian hemorrhage resulting in ovarian infarction may lead to a life-threatening intraperitoneal hemorrhage in women with bleeding disorders such as aplastic anemia (AA). Moreover, it is seen as ovarian tumors in the diagnosis. The authors report a clinical case with the aim of sharing our experiences and exploring the ways to diagnose, treat, and avoid ovarian hemorrhage. PATIENTS CONCERNS: A 48-year-old woman with AA had suffered from a serious abdominal distension for the past 24 hours, which had occurred intermittently for the past 15 years. DIAGNOSES: Pelvic ultrasonography had revealed a large anechoic area of fluid in the abdomen without any sign of primary hemorrhage each time she had experienced an episode over the past 15 years. The volume of pelvic fluid had decreased after anti-inflammatory and hemostatic treatment. At presentation, the abdominal computed tomography suggested an ovarian tumor with a massive hemoperitoneum (a right ovarian mass, 5.7 × 5.0 × 5.0 cm in size, with a large amount of abdominal and pelvic fluid). INTERVENTIONS: Surgery was performed with respect to the bilateral uterine adnexa. On laparotomy, there were blood clots of approximately 6.0 × 6.0 × 5.0 cm surrounding the right ovary and approximately 400 mL bloody fluid in the abdomen. OUTCOMES: The patient recovered without incident and was transferred to a hematology ward 1 week later. Postoperative pathology confirmed hemorrhagic infarction of the right ovary. LESSONS: In conclusion, continuous ovarian bleeding can cause ovarian infarction to women with bleeding disorders and it may be confused with an ovarian tumor. Moreover, an earlier ovariectomy procedure under stable conditions or treatment with gonadotropin-releasing hormone that prevent bleeding via ovulation suppression may be effective for such cases.