Zhongping Cheng

Laparoscopic Uterine Artery Occlusion Combined with Myomectomy for Uterine Myomas

We sought to evaluate the clinical feasibility and mid- to long-term effects of laparoscopic uterine artery occlusion before myomectomy in the treatment of uterine myomas. A total of 566 patients with uterine myoma were treated by laparoscopic uterine artery occlusion before myomectomy from October 2001 through July 2007. Mean blood loss was 88.2 +/- 52.7 mL (95% CI 82.7-93.8). The highest postoperative temperature was 37.8 +/- 0.3 degrees C, and the postoperative morbidity was 5.7% (32/566). Number of days to the return of bowel movement was 1.9 +/- 0.5d and in hospital stay after surgery was 7.7 +/- 2.5d. Complications included 2 instances of subcutaneous emphysema, 1 of vaginal bleeding, and 3 of mild intestinal obstruction. At a median of 26.3 months (range 6-69 months) of follow-up, the rate of myoma recurrence was 3.0% (15/517), uterus volume reduction was 48.9%, and correction of menstruation abnormality was 97.1% (502/517). Laparoscopic uterine artery occlusion before myomectomy can expand myomectomy indications with better results.

LPS/TLR4-mediated stromal cells acquire an invasive phenotype and are implicated in the pathogenesis of adenomyosis

The present study tested whether the LPS/TLR4 signal pathway in endometrial stromal cells is essential for the pathogenesis of adenomyosis. We tested the expression of TLR4, MD2 in the endometrium without adenomyosis (CE), the eutopic endometrium with adenomyosis (EuE) and the ectopic endometrium with adenomyosis (EE). We isolated the stromal cells from CE, EuE and EE (CESC, EuESC, EESC), treated with lipopolysaccharide (LPS) and TLR4 antagonist and detected the cell viability. And we also measured the key protein of the TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells. We found that the viability of experimental cells treated with LPS was significantly greater than that of the non-treated cells, blocked by the TLR4 antagonist VIPER. TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells stimulated by LPS, and it was inhibited by VIPER. This study suggested that stromal cells were activated by the TLR4 signalling pathway, which processed the cellular inflammatory proliferation and invasive growth involved in the pathogenesis of adenomyosis.

Controlled Clinical Trial Assessing the Effect of Laparoscopic Uterine Arterial Occlusion on Ovarian Reserve

STUDY OBJECTIVE To assess the effect on ovarian reserve function after laparoscopic uterine artery occlusion (LUAO) compared with laparoscopic surgery supracervical hysterectomy (LSH) and laparoscopic myomectomy (LM). DESIGN Prospective cohort study (Canadian Task Force classification II-1). SETTING Hospital with experience in gynecologic minimal access surgery. PATIENTS Ninety patients with uterine myomas operated on from August through December 2007. INTERVENTION Ninety patients were divided into 3 groups of 30 patients each: the study group underwent LUAO and myomectomy (LUAO-M), control group 1 underwent LSH, and control group 2 underwent LM only. MEASUREMENTS AND MAIN RESULTS Blood samples were collected before surgery and at 1, 3, and 6 months postoperatively. Concentrations of follicle-stimulating hormone (FSH), leuteinizing hormone (LH), and estradiol (EZ) were determined using an immunoassay, and serum inhibin B (INHB) concentration was evaluated using an enzyme-linked immunosorbent assay. No significant differences in preoperative hormone concentrations between the 3 groups were found (p>.05). In the LSH group, FSH, LH, and E2 concentrations were significantly increased, whereas the INHB concentration was significantly decreased at 1 month postoperatively (p<.05); after 3 months, only the INHB concentration was significantly decreased (p<.05). However, in the LOUA-M and LM groups, there were no significant differences between preoperative and postoperative hormone concentrations (p>.05). Serum concentrations of FSH, LH, and INHB in the LSH group were significantly different from those in the study group at 1 and 3 months postoperatively (p<.05); however, the differences in postoperative hormone concentrations between the study group and the LM group were not significant (p>.05). CONCLUSION At short-term follow-up, no significant effect on ovarian reserve in patients with myoma who underwent LUAO was found.

Clinical Application and Midterm Results of Laparoscopic Partial Resection of Symptomatic Adenomyosis Combined with Uterine Artery Occlusion

STUDY OBJECTIVE To examine the clinical application of laparoscopic partial resection of symptomatic adenomyosis combined with uterine artery occlusion (UAO). DESIGN Retrospective cohort study (Canadian Task Force classification III). SETTING A district hospital. PATIENTS A total of 37 patients with symptomatic adenomyosis who had indication for surgical intervention but needed conservative treatment. INTERVENTION Uterine artery occlusion combined with partial resection of adenomyosis via laparoscopy. MEASUREMENTS AND MAIN RESULTS From July 2003 through October 2005, 37 patients with symptomatic adenomyosis were treated by UAO combined with partial resection of adenomyosis via laparoscopy. All patients were followed up at 1, 6, and 12 months after the operation to estimate the volume of the uterus and changes of symptoms including pelvic pain and abnormal bleeding. Patients also were asked to participate in a clinical interview every year thereafter. No severe complications were noted during the surgical procedure or follow-up. The mean surgical time was 115.7 +/- 27.5 minutes (Mean +/- SD, 61-171 minutes), the mean blood loss was 80.0 +/- 35.2 mL (50-150 mL), and the median highest body temperature after the procedure was 38 degrees C (range 37.4 degrees C-39 degrees C). The postoperative fever morbidity was 10.8% (4/37). Improvement of menorrhagia occurred in all of 37 and 35 of 37 for dysmenorrhea. Hysterectomy was carried out in 2 patients because of persistence of dysmenorrhea. Pictorial blood loss assessment chart was used to measure menstrual blood loss and an 11-point numeric rating scale was used to evaluate the pain intensity during menstruation. The postoperative median scores of menorrhagia were 58, 56, and 59 at 1, 6, and 12 months, respectively, compared with 158 before treatment. Significant improvement occurred (p <.001, p <.001, p <.001), compared with each other, no significant difference existed (1 vs 6 months, p =.720; 6 vs 12 months, p =.992; 1 vs 12 months, p =.709). The postoperative median scores of dysmenorrhea were 7, 5, and 4 at 1, 6, and 12 months. Respectively, compared with 8 before operation; significant symptom lessening occurred (p <.001, p <.001, p <.001). Comparing with each other, significant difference also existed (1 vs 6 months, p <.001; 6 vs 12 months, p <.001; 1 vs 12 months, p =.0018). The volume of the uterus before procedure was 224.6 +/- 48.7 cm(3) (156.0-336.1 cm(3)). At 6 and 12 months it was 169.2 +/- 78.1 cm(3) (118.4-218.2 cm(3)) and 91.6 +/- 28.4 cm(3) (43.1-127.5 cm(3)), respectively. At 6 months after surgery the volume of uterus shrank 24.7% compared with preoperative volume; shrinkage rate was 59.2% at 12 months after surgery. A continuous decrease occurred (p <.001, p <.001, p <.001). CONCLUSION Laparoscopic partial resection of adenomyosis combined with UAO is an effective treatment modality for symptomatic adenomyosis, but further controlled studies with large samples and long-term follow-up is needed for a decisive conclusion.

ARHGAP10, downregulated in ovarian cancer, suppresses tumorigenicity of ovarian cancer cells.

Rho GTPase-activating proteins (RhoGAPs) are implicated in the development and progression of ovarian cancer. ARHGAP10 is a member of RhoGAP proteins and inactivates Cdc42 by converting GTP-bound form to GDP-bound form. Here, we aimed to evaluate ARHGAP10 expression profile and functions in ovarian cancer. The decreased expression of ARHGAP10 was found in 77.3% (58/75) of ovarian cancer tissues, compared with their non-tumorous counterparts. Furthermore, overall survival in ovarian cancer patients with higher expression of ARHGAP10 was longer than those with lower expression. Ectopic expression of ARHGAP10 in two ovarian cancer cell lines with lower expression of ARHGAP10 (A2780 and HO-8910) dramatically suppressed cell proliferation in vitro. In nude mice, its stable overexpression significantly inhibited the tumorigenicity of A2780 cells. We further demonstrated that overexpression of ARHGAP10 significantly inhibited cell adhesion, migration and invasion, resulted in cell arrest in G1 phase of cell cycle and a significant increase of apoptosis. Moreover, ARHGAP10 interacted with Cdc42 and overexpression of ARHGAP10 inhibited the activity of Cdc42 in A2780 cells. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that KEGG cell cycle, replication and base excision repair (BER) pathways were correlatively with the ARHGAP10 expression, which was further confirmed in ovarian cancer cells by western blotting. Hence, ARHGAP10 may serve as a tumor suppressor through inactivating Cdc42, as well as inhibiting cell cycle, replication and BER pathways. Our data suggest an important role of ARHGAP10 in the molecular etiology of cancer and implicate the potential application of ARHGAP10 in cancer therapy.

The Expression of Toll-like receptors in eutopic and ectopic endometrium and its implication in the inflammatory pathogenesis of adenomyosis.

In this study, we investigated the expression profiles of Toll-like receptors(TLRs) in eutopic endometrium(EU) and ectopic endometrium(EC) and its implication in the inflammatory pathogenesis of adenomyosis. Thirty adenomyosis patients who underwent laparoscopy were recruited in this study. We tested the mRNA and protein expression of TLRs, and the mRNA expression of IL-6 and IL-8 in EU and EC of adenomyosis patients, and control endometrium without adenomyosis(CE). We found that the mRNA expression of IL-6 and IL-8 in EU was significantly higher than that in CE, and was the highest in EC (P < 0.01). The mRNA and protein expression of TLRs were higher in EU, with the expression of TLR1-6, 8 and 9 being significantly higher in EU than in CE, and were the highest in EC (except TLR6) (P < 0.05 or P < 0.01). Pearson correlation analysis showed that the expression of TLR1, 2, 4, 5 and 9 in EU and EC was positively correlated with that of IL-6 and IL-8 (P < 0.00139). This study suggested that adenomyosis was a state of inflammatory pathology. High expression of TLRs in EU and EC were positively correlated with IL-6 and IL-8, which may be involved in the inflammatory pathogenesis of adenomyosis.

Appearance of Inflammation in Peripheral Blood during Menstrual Cycles in Women of Childbearing Age

Background: Chronic inflammation has been reported as a triggering and driving factor in the pathogenesis of various diseases and is believed to be closely associated with tumor pathogenesis. In this study, we aimed to explore the changes of the inflammatory stress-related indexes during the menstrual period. Methods: Cytokines and tumor-associated carbohydrate antigens from 76 childbearing-age women during the follicular phase, luteal phase, and menstrual period were measured. Results: The expression of inflammatory indexes, such as platelets (PLT), lymphocytes (Lym), the percentage of Lym (Lym%), neutrophils (Neu), the percantage of Neu (Neu%), neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6), and cancer antigen 125 (CA125), reached the highest level during the menstrual period. Conclusions: Female genital organs are under inflammatory stress during menstruation, which hints that the changes of the inflammatory state of the body play an important role in the pathogenesis of diseases.

TRIM52 plays an oncogenic role in ovarian cancer associated with NF-kB pathway

Emerging evidence suggests that the members of the tripartite motif (TRIM) family play a crucial role in cancer development and progression. The purpose of the study was to explore TRIM52s role in tumorigenesis and its potential molecular mechanism in ovarian cancer. The study demonstrated that knockdown of TRIM52 in SKOV3 and CAOV3 cells inhibited ovarian cancer cell invasion, migration, and proliferation, and induced cell apoptosis. On the contrary, overexpression of TRIM52 in HO8910 cells showed contrary results. Further, overexpression of TRIM52 enhanced the expression of phosphorylated IKKβ and IKBα proteins and nuclear protein P65, which implied the activation of NF-kB signal pathway. Knockdown of TRIM52 downregulated the mRNA and protein levels of NF-kB signal downstream effectors of the NF-kB pathway, including MMP9, Bcl2, IL8, and TNFα, but upregulated caspase-3 expression. These results suggested that activation of the NF-kB pathway is involved in TRIM52-mediated regulation in ovarian cancer. The nude mice study further confirmed that knockdown of TRIM52 blocked tumor growth, inhibited cell proliferation, and promoted cell apoptosis. Our data strongly suggested that TRIM52 plays an oncogenic role in ovarian cancer development associated with the NF-kB signal pathway and may be a potential target for cancer therapy.

Eutopic/ectopic endometrial apoptosis initiated by bilateral uterine artery occlusion: A new therapeutic mechanism for uterus-sparing surgery in adenomyosis

The objective of the present study was to investigate differences in the expression of apoptosis-related factors in the eutopic and ectopic endometrium (EuE/EE) in women with adenomyosis before and after laparoscopic bilateral uterine artery occlusion (LUAO). Ten patients with uterine adenomyosis who received LUAO were selected as the research subjects, from whom EuE and EE tissues were obtained before and after LUAO and detected for the expression of apoptosis-related molecules in EuE and EE by PT-PCR and Western blot, and changes in the mitochondrial structure by electron microscopy. Normal endometrial stromal cells (NESC), and EuE/EE stromal cells in women with adenomyosis were cultured in a 1% O2, 5% CO2 incubator to establish a physical anoxia state in an in vitro stromal cell model. The expression of apoptosis-related molecules was observed at 0, 6, 12, 24 and 48h of hypoxic. The results showed that the expression of apoptosis-related factors in EuE and EE were increased significantly after LUAO and under hypoxic conditions in vitro, suggesting that transient ischemia and hypoxia were involved in the apoptosis of adenomysis lesions, and that uterine artery occlusion could remove adenomyosis lesions on tissue/cell level by cytoreduction, thus reaching the goal of treating adenomyosis effectively.

Berberine inhibits growth and inflammatory invasive phenotypes of ectopic stromal cells: Imply the possible treatment of adenomyosis

Adenomyosis is a common chronic gynecological disorder with some tumor-like properties, including aberrant proliferation, invasion and migration. Berberine (BBR) is an isoquinoline derivative alkaloid with diverse pharmacological activities for the treatment of a wide variety of diseases. However, the effect of BBR on adenomyosis has not been understood. This study was to evaluate the potential therapeutic effect of BBR on ectopic endometrial stromal cells (EESCs) isolated from patients with adenomyosis. Our data showed that BBR significantly inhibited the proliferation and viability of eutopic endometrial stromal cells (EuESCs) and EESCs, while slightly affected the growth of normal endometrial stromal cells (NESCs). BBR markedly exhibited a growth inhibitory effect on EESCs by triggering apoptosis and cell cycle arrest, and alleviating the expression of inflammatory invasive phenotypes (IL-6, IL-8, TGF-β, EGF, VEGF, and MMP2). The alleviation of inflammatory invasive phenotypes partly involved nuclear translocation of NFκB/p65 and stat3 activation. Taken together, BBR markedly inhibits the growth of EESCs and might be a promising new strategy for the treatment of adenomyosis.