Min Xue

Etiology, treatment, and reproductive prognosis of women with moderate-to-severe intrauterine adhesions

To analyze data from the hysteroscopic adhesiolysis of moderate‐to‐severe intrauterine adhesions (IUAs), and to review the disease etiology, changes in menstruation, uterine recovery, and reproductive prognosis of women after comprehensive therapy.

High expression of octamer transcription factor 1 in cervical cancer

Cervical carcinoma is the second most prevalent malignancy in females worldwide. The crucial etiologic factors involved in the development of cervical carcinoma include infection with papillomavirus, and the structural or functional mutation of oncogenes and tumor suppressor genes. The abnormal change of octamer transcription factor 1 (OCT1) is associated with tumor progression and a poor patient survival rate. However, little is known regarding the effect of OCT1 in cervical cancer. In the present study, flow cytometry, western blot analysis and quantitative polymerase chain reaction (qPCR) were peformed to identify differentially expressed OCT1 in cervical cancer tissue and adjacent non-cancerous tissues. The normalized OCT1 gene expression in cervical cancer was 5.98 times higher compared with the adjacent non-cancerous tissues. Western blot analysis and flow cytometry assessed the levels of OCT1 protein. The results of these two differential techniques showed that the protein expression level of OCT1 was greater in cervical cancer tissues, which corresponded with the qPCR results. Finally, as OCT1 is a potential target gene for microRNA (miR)-1467, -1185, -4493 and -3919, their expression levels were analyzed in cervical cancer tissues and adjacent non-cancerous tissues; they were downregulated by ~45% in the cervical cancer samples. The results of the present study showed that OCT1 is highly expressed in cervical cancer tissues and indicated that OCT-1 may be significant in cervical cancer.

Defective antioxidant systems in cervical cancer

Cervical cancer remains a great problem for woman health, as it is the second deadly cancer of females worldwide. The infection of human papilloma virus (HPV) is the major risk factor for this cancer, although several other factors are also associated. Oxidative stress or antioxidant deficiency has been frequently identified to be associated with cervical cancer. Defects in the antioxidant enzyme systems are reported to play important role behind this antioxidant deficiency, which is responsible for the production of reactive oxygen species and ultimately, DNA damage in cervical cells. In response, cells become more vulnerable to HPV infection for cervical cancer development. Recently, antioxidant therapies or dietary supplementation of antioxidants have gained considerable interests in the cervical cancer treatment. In this study, we have reviewed the association of defective antioxidant systems and cervical cancer development. The recent advances in both of the basic and clinical research focusing on possible antioxidant therapy have also been discussed.

Fra-1 is downregulated in cervical cancer tissues and promotes cervical cancer cell apoptosis by p53 signaling pathway in vitro.

Cervical cancer is a potentially preventable disease; however, it is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. Cervical cancer is thought to develop through a multistep process involving virus, tumor suppressor genes, proto-oncogenes and immunological factors. It is known that human papillomavirus (HPV) infection is necessary but insufficient to cause malignancy. At present, the etiology of cervical carcinoma remains poorly understood. In this study, we found that the expression of FOS-like antigen-1 (Fra-1) gene was downregulated in cervical cancer compared with the adjacent non-cancerous tissues by RT-qPCR, immunohistochemistry (IHC) and western blotting techniques. To uncover the effect of Fra-1 on cervical cancer, we tested and confirmed that Fra-1 significantly inhibited the proliferation of HeLa cells by MMT assays in vitro. At the same time, overexpression of Fra-1 promoted apoptosis of HeLa cells. To explore the possible mechanism of Fra-1 in cervical cancer, we tested the expression levels of key molecules in p53 signaling pathway by western blotting technology. The results showed that p53 was downregulated in cervical cancer compared with the adjacent non-cancerous tissues, but MDM2 proto-oncogene, E3 ubiquitin protein ligase (MDM2) was upregulated in cervical cancer. In vitro, the p53 was upregulated and MDM2 was downregulated in HeLa cells with Fra-1 overexpression. In summary, our results suggested that Fra-1 expression is low in cervical cancer tissues and promotes apoptosis of cervical cancer cells by p53 signaling pathway.

High-intensity focused ultrasound combined with suction curettage for the treatment of cesarean scar pregnancy.

AbstractThe aim of this study was to retrospectively evaluate the safety and feasibility of high-intensity focused ultrasound (HIFU) treatment combined with suction curettage under hysteroscopic guidance for cesarean scar pregnancy (CSP).Fifty-three patients with definite CSP were treated with HIFU followed by suction curettage under hysteroscopic guidance. All the patients received 1 session of HIFU ablation under conscious sedation. Suction curettage under hysteroscopic guidance was performed at an average of 2.9 (range: 1–5) days after HIFU ablation. Blood flow of pregnancy tissue before and after HIFU, intraoperative blood loss in suction curettage and hysteroscopy procedure, time for &bgr;-human chorionic gonadotropin (&bgr;-hCG) to return to normal level, and time for normal menstruation recovery were recorded.Immediately after HIFU treatment, color Doppler ultrasound showed that the fetal cardiac activity disappeared and the blood flow in the pregnancy tissue significantly decreased. All the patients underwent suction curettage under hysteroscopic guidance after the treatment of HIFU, the median volume of blood loss in the procedure was 20 mL (range: 10–400 mL). The average time for menstruation recovery was 35.1 ± 8.1 (range: 19–60) days. The average time needed for serum &bgr;-hCG to return to normal levels was 27.5 ± 6.4 (range: 12–40) days. The average hospital stay was 7.8 ± 1.5 (range: 5–11) days.Based on our results, it appears that HIFU combined with suction curettage under hysteroscopic guidance is safe and effective in treating patients with CSP at gestational ages <8 weeks.

A Randomized Controlled Trial on the Efficacy and Safety of a New Crosslinked Hyaluronan Gel in Reducing Adhesions after Gynecologic Laparoscopic Surgeries

STUDY OBJECTIVE To evaluate the safety and efficacy of a new crosslinked hyaluronan (NCH) gel in reducing postoperative adhesions. DESIGN Randomized controlled trial (Canadian Task Force classification I). SETTINGS Seven departments of obstetrics and gynecology in China. PATIENTS A total of 216 women scheduled for gynecologic laparoscopic surgery for primary removal of adhesions, myomas, ovarian cysts, or endometriotic cysts. INTERVENTIONS Patients were randomized to receive either NCH gel or saline with 1:1 allocation. MEASUREMENTS AND MAIN RESULTS All patients were evaluated using a modified American Fertility Society (mAFS) scoring system for the incidence, extent, and severity of pre-existing and postoperative adhesions at the 10 anatomic sites of ovaries/tubes and at the expanded 23 or 24 anatomic sites throughout the abdominopelvic cavity by laparoscopy. A total of 215 randomized patients were treated with either saline solution (108 of 108) or NCH gel (107 of 108), composing the full analysis set (FAS), and 196 patients (94 of 108 in the saline control group and 102 of 108 in the NCH gel group) completed the entire study, composing the per protocol set (PPS). The postoperative incidence of moderate or severe adhesions evaluated at the 10 sites (the primary endpoint for efficacy) was 27.7% in the control group and 9.8% in the NCH gel group, a difference of 14.4% (95% confidence interval [CI], 2.6%-20.6%) in the PPS, and 37.0% in the control group and 14.0% in the NCH gel group, a difference of 20.0% (95% CI, 8.9%-26.8%) in the FAS. The postoperative incidence of moderate or severe adhesions evaluated at the 24 sites was also significantly lower in the NCH gel group compared with the control group (5.9% vs 14.9%; p = .036) in the PPS. Also in the PPS, the NCH gel group had significantly lower postoperative adhesion scores of severity, extent, and mAFS: 60.0%, 50.8%, and 76.9%, respectively (median scores of the 10 sites; p = .002) and 48.5%, 50.0%, and 72.2% (median scores of the 24 sites; p = .001) lower than those recorded in the control group. No serious adverse events were observed, and the safety profile of NCH gel was comparable to that of saline control. CONCLUSION This study demonstrates that NCH gel is safe and significantly reduces adnexal adhesion formation and global adhesion formation throughout the abdominopelvic cavity after gynecologic laparoscopic surgery.

MiR-200b promotes the cell proliferation and metastasis of cervical cancer by inhibiting FOXG1.

BACKGROUND Previous studies have revealed the important role of miR-200b in cancer biology, including its upregulation in cervical cancer. However, miR-200b function in cervical cancer progression remains unclear. Thus, this study aims to explore the functional role of miR-200b in cervical cancer development, involving its potential regulation on FoxG1, one transcriptional repressor. METHODS Thirty paired cervical cancer samples were used to analyze the expression of miR-200b and FoxG1 by real time PCR and western blot analysis. Further gain- and loss-of-function studies were performed to validate FoxG1 as one miR-200b target, in line with luciferase report assays. MiR-200b silence was also conducted to observe its regulation on cell viability, migration and invasion in vitro, while tumor growth in vivo was tracked through the delivery of miR-200b inhibitor. RESULTS MiR-200b upregulation was confirmed in cancer tissues or cells as compared to normal controls, while FoxG1 downregulation was observed and then FoxG1 was definitely validated as one miR-200b target. Further in vitro studies showed that enforced miR-200b downregulation induced the decrease of cell ability, with increased cell apoptosis, and attenuated ability of cell migration and invasion in both HeLa and C33A cells, while further inhibition of FoxG1 expression could reverse all these changes. In addition, miR-200b silence in vivo strongly inhibited tumor growth. CONCLUSION Upregulated miR-200b in cervical cancer was proven to show positive regulation on cervical cancer development by directly targeting FoxG1. Moreover, miR-200b silence was proposed to inhibit tumor growth in vivo, implying its therapeutic value in cervical cancer treatment.

P16INK4A is required for cisplatin resistance in cervical carcinoma SiHa cells

Cervical cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer-related mortality in females worldwide, accounting for 10–15% of cancer-related mortalities. Cytological screening and DNA testing for high-risk human papillomavirus (HPV) types have markedly decreased the rates of cervical cancer in developed countries, however, for vulnerable populations without access to health care, cervical cancer remains a considerable problem. Chemotherapeutic agents such as cisplatin (DDP) are considered as first-line treatment for cervical carcinoma. Although initially patients often exhibit high responsiveness, the majority eventually develop DDP resistance. However, the mechanisms underlying this process remain unclear. Furthermore, patients with metastatic cancer and those exhibiting persistent or recurrent disease after platinum-based chemoradiotherapy have limited options and thus, non-platinum combination chemotherapy has been proposed as a strategy to circumvent platinum resistance, however, novel therapeutic strategies are required. In the present study, P16 expression was analyzed by quantitative-polymerase chain reaction and western blot analysis in SiHa and SiHa-DDP cells and the interaction between P16 and CDK4 was detected via co-immunoprecipitation. In addition, the proliferation and apoptosis rates of P16 knockdown SiHa-DDP cells were measured by MTT assay and Annexin V flow cytometry and the subsequent changes in cyclin D1 and pRb expression were analyzed by western blot analysis. In this study, a high level of P16INK4A expression and its enhanced interaction with cyclin-dependent kinase-4 in cervical carcinoma DDP-resistance cells (SiHa-DDP) was identified, which was associated with the inactivation of phosphorylated retinoblastoma protein (pRb). Knockdown of P16INK4A significantly induced cellular growth, when compared with the control cells, via the upregulation of pRb, and also promoted apoptosis following treatment with DDP. The results of this study indicated, for the first time, that P16INK4A is required for DDP resistance in cervical carcinoma SiHa cells and, thus, these results may lead to the development of novel strategies for the treatment of chemoresistant cervical carcinoma.

Analysis of the efficacy of three treatment options for cesarean scar pregnancy management

To assess three different methods in treating patients with cesarean scar pregnancy (CSP).

The definition, aetiology, presentation, diagnosis and management of previous caesarean scar defects

Caesarean sections are the most commonly performed surgical procedures involving the uterus in fertile women. Typically, this surgery involves a transverse incision in the anterior lower uterine segment. The incidence of caesarean sections is on the increase worldwide, and consequently, the complications associated with them are becoming more common. One such complication that is gaining more attention is previous lower uterine segment caesarean scar defect (PCSD). In this review, we sought to explore the definition, aetiology, presentation, diagnosis and management of PCSD.