GALNT14 regulates ferroptosis and apoptosis of ovarian cancer through the EGFR/mTOR pathway.

Background: Chemoresistance usually occurs in ovarian cancer. We aimed to explore the mechanisms of chemoresistance. Methods: Western blotting assay was used to detect the expression of GALNT14. Further cell function experiments were performed to investigate the effect of GALNT14 in ovarian cancer. Results: GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. Finally, an additive effect promoting cell death occurs with a combination of an mTOR inhibitor and cisplatin. Conclusion: Our study might provide a promising method to overcome cisplatin resistance for patients with ovarian cancer.

Intratumoral levels and prognostic significance of Fusobacterium nucleatum in cervical carcinoma.

Growing evidence suggests that microbes can influence the onset of cancer and its consequent development. By researching samples from patients afflicted by cervical cancer, we aimed to explore the associated dynamics and prognostic value of intratumoral levels of F. nucleatum. We used qPCR to analyze tumor tissues obtained from 112 cervical cancer patients in order to characterize the levels and influences of intratumoral levels of the F. nucleatum. Especially for recurrent tissues, there was a distinct observation of higher levels of F. nucleatum in cervical cancer. Patients with high burdens of F. nucleatum intratumoral infiltration exhibited correspondingly poor rates of both overall survival and progression-free survival. Measures of the levels of F. nucleatum were found to have been reliable independent prognostic factors that could predict rates of PFS for afflicted patients (HR = 4.8, 95%CI = 1.2-18.6, P = 0.024). Notably, the levels ofF. nucleatum were positively correlated with tumor differentiation. Cancer cells from patients with relatively high levels of F. nucleatum were observed to possess the characteristics of cancer stem cells (CSCs). We propose that F. nucleatum might be one potential cervical cancer diagnostic and prognostic biomarker, and these findings will help to provide a sound rationale and merit for further study of this bacterium.

Intravenous leiomyomatosis with different surgical approaches: Three case reports.

BACKGROUND: Intravenous leiomyomatosis (IVL) is a rare and complicated disease, which requires surgery by a multidisciplinary team. However, the optimal surgical approach has not been determined. CASE SUMMARY: Here we report three cases of IVL treated with different surgical approaches. All patients presented with circulation symptoms. Two patients had lower extremity edema and the other had cardiopalmus. The diagnosis of IVL was confirmed based on the imagining examinations and pathological findings. All patients underwent surgical treatment and were discharged without any complications. CONCLUSION: Preoperative examination is crucial for surgical planning and surgical approach is dependent on the patient's condition and tumor involvement.

The value of hysteroscopic management of cesarean scar pregnancy: a report of 44 cases.

OBJECTIVE: With the incidence of cesarean scar pregnancy (CSP) rising, the reports of serious adverse outcomes of it have increased gradually. The management of CSP remains an inadequately explored clinical field, and there is no consensus on it presently. The present study was performed to investigate the efficacy and safety of operative hysteroscopy in the diagnosis and treatment of CSP. MATERIALS AND METHODS: Forty-four patients with CSP underwent operative hysteroscopy for removal of scar ectopic pregnancy in our institution. Among them, hysteroscopy was combined with laparoscopy in two patients, three cases with massive hemorrhage were pretreated with bilateral uterine artery embolization before hysteroscopic surgery, and four patients were pretreated with mifepristone (200 mg for 3 days) and methotrexate (25 mg for 2 days). Clinical data, serum ß-human chorionic gonadotropin, myometrial thickness, residual conceptus, cesarean scar defect, operation time, blood loss, and hospital stay were recorded. RESULTS: All of the ectopic gestations were removed entirely by operative hysteroscopy. Mean operation time was 34.8±16.5 minutes (range 20-120 minutes), and mean blood loss was 35.3±24.4 mL (range 5-100 mL). The mean hospital stay was 5.0±3.01 days (range 1-19 days). Cesarean scar defect could be diagnosed in 70% (31/44) of patients, while in 20/32 cases (63%), a conceptus remained after uterine curettage only was performed. CONCLUSION: Operative hysteroscopy might be recommended as a first-line treatment modality for patients with a cesarean scar ectopic pregnancy, especially when myometrium thickness between bladder and gestational sac is more than 3 mm.

Treatment of Early Stage Endometrial Cancer by Transumbilical Laparoendoscopic Single-Site Surgery Versus Traditional Laparoscopic Surgery: A Comparison Study.

To compare the outcomes of transumbilical laparoendoscopic single-site surgery (TU-LESS) versus traditional laparoscopic surgery (TLS) for early stage endometrial cancer (EC).We retrospectively reviewed the medical records of patients with early stage EC who were surgically treated by TU-LESS or TLS between 2011 and 2014 in a tertiary care teaching hospital. We identified 18 EC patients who underwent TU-LESS. Propensity score matching was used to match this group with 18 EC patients who underwent TLS.All patients underwent laparoscopic-assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy by TU-LESS or TLS without conversion to laparoscopy or laparotomy. Number of pelvic lymph nodes retrieved, operative time and estimated blood loss were comparable between 2 groups. Satisfaction values of the cosmetic outcome evaluated by the patient at day 30 after surgery were significantly higher in TU-LESS group than that in TLS group (9.6 ±â€Š0.8 vs 7.5 ±â€Š0.7, P < 0.001), while there was no statistical difference in postoperative complications within 30 days after surgery, postoperative hospital stay, and hospital cost.For the surgical management of early stage EC, TU-LESS may be a feasible alternative approach to TLS, with comparable short-term surgical outcomes and superior cosmetic outcome. Future large-scale prospective studies are needed to identify these benefits.

[Longitudinal analysis of vaginal microbiota in women with recurrent vulvovaginal candidiasis].

OBJECTIVE: To investigate the vaginal flora in patients with recurrent vulvovaginal candidiasis (RVVC). METHODS: Vaginal swabs were collected at different time points from 6 RVVC patients and 5 healthy women of child-bearing age. The dynamic changes, microbiota composition, alpha diversity and beta diversity in the two groups were assessed by analyzing the 16S rRNA V4 hypervariable region amplified from the total genomic DNA from the swabs. RESULTS: Lactobacillus was the predominant species in healthy women with similar proportions of L.iners and L.crispatus; small proportions of Gardnerella, Prevotella and other genus were also detected. In some healthy women, the vaginal flora showed a high relative abundance of anaerobic bacteria such as Gardnerella, Prevotella, Atopobium, Sneathia. Compared with the healthy women, patients with RVVC showed a significantly reduced diversity of vaginal flora, where L.iners was the predominant species and the content of L.crispatus decreased significantly. In healthy women, the vaginal flora fluctuated with the menstrual cycle, and the fluctuation was the most prominent during menstruation; the dominant species either alternated regularly or maintain an absolute superiority in the menstrual cycle. The vaginal flora showed attenuated fluctuation in women with RVVC, were highly conserved within the menstrual cycle, and maintained a similar composition in the episodes and intermittent periods. CONCLUSION: The vaginal flora of RVVC patients do not undergo regular variations with the menstrual cycle and shows a similar composition between the episodes and intermittent periods. Promoting the production of L.iners or inhibiting the colonization of L.crispatus to restore the composition of the vaginal flora may help in the treatment of RVVC.

Diverse vaginal microbiomes in reproductive-age women with vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases, and there are controversial reports regarding the diversity of the associated vaginal microbiota. We determined the vaginal microbial community in patients with VVC, bacterial vaginosis (BV), and mixed infection of VVC and BV using Illumina sequencing of 16S rRNA tags. Our results revealed for the first time the highly variable patterns of the vaginal microbiome from VVC patients. In general, the alpha-diversity results of species richness and evenness showed the following order: normal control < VVC only < mixed BV and VVC infection < BV only. The beta-diversity comparison of community structures also showed an intermediate composition of VVC between the control and BV samples. A detailed comparison showed that, although the control and BV communities had typical patterns, the vaginal microbiota of VVC is complex. The mixed BV and VVC infection group showed a unique pattern, with a relatively higher abundance of Lactobacillus than the BV group and higher abundance of Prevotella, Gardnerella, and Atopobium than the normal control. In contrast, the VVC-only group could not be described by any single profile, ranging from a community structure similar to the normal control (predominated with Lactobacillus) to BV-like community structures (abundant with Gardnerella and Atopobium). Treatment of VVC resulted in inconsistent changes of the vaginal microbiota, with four BV/VVC samples recovering to a higher Lactobacillus level, whereas many VVC-only patients did not. These results will be useful for future studies on the role of vaginal microbiota in VVC and related infectious diseases.

[Laparoendoscopic single-site surgery for gynecologic malignancy: the first report in China].

OBJECTIVE: To report the first case of laparoendoscopic single-site surgery (LESS) for gynecologic malignancy in China and discuss the application of LESS in minimally invasive gynecologic surgery. METHODS: A 57-year-old postmenopausal woman presented with vaginal bleeding for 5 years and diagnostic curettage revealed endometrial cancer. Staged LESS for endometrial cancer was performed using a single multiple-channel port (Tri-port) inserted through a solitary 2.5 cm upper umbilicus incision. RESULTS: The operation was completed successfully. The total operative time was 4.5 h, the duration of the LESS procedure was 4.0 h, and the establishment of the operative access took 1.0 h. No other port incision or transfer to open procedure was needed. The intraoperative blood loss was 100 ml. Bowel peristalsis and micturition recovered 2 days after the operation, and the peritoneal drainage tube was removed 4 days after the operation without vaginal bleeding. No obvious scar was left on the surface of umbilicus. CONCLUSION: LESS can be a promising minimally invasive approach to effective management of benign and malignant gynecological diseases.

[Transumbilical laparoendoscopic single-site surgery-assisted vaginal hysterectomy: initial report in South China].

OBJECTIVE: To report the first case of transumbilical laparoendoscopic single-site surgery-assisted vaginal hysterectomy in South China, and discuss its feasibility and safety. METHODS: A 42-year-old woman with multiple myoma of the uterus underwent laparoendoscopic single-site surgery-assisted vaginal hysterectomy performed using a single multiple-channel port inserted through a solitary 2 cm upper umbilicus incision. RESULTS: The total operative time was 3 h, and duration of the laparoendoscopic procedure was 2 h. The surgery was completed uneventfully without an additional port incision or transfer to open surgery. The intraoperative blood loss was 100 ml. Bowel peristalsis was recovered 3 days after the operation. The vaginal stump and abdominal incision healed smoothly without occurrence of vaginal bleeding. CONCLUSION: With the development of surgical instruments and improvement of the surgeons' skills, laparoendoscopic single-site surgery, due to its invasiveness, can be a promising approach to the management of gynecological disease including gynecological malignant tumors.

[Small interference RNA targeting nuclear factor-kappaB inhibits endometriotic angiogenesis in chick embryo chorioallantocic membrane].

OBJECTIVE: To investigate the effect of small interference RNA (siRNA) targeting nuclear factor-kappaB (NF-kappaB) on endometriosis. METHOD: The eutopic endometrium of women with endometriosis were transplanted into the nonvascular region of 8-day-old chicken embryo chorioallantocic membrane (CAM), and the effects of NF-kappaB p65 siRNA on the vascularization and endometriotic lesion formation were tested with proper controls. RESULTS: Transplantation of the endometrium onto the CAM resulted in a strong angiogenic response in the chicken tissue. The angiogenesis was significantly reduced and endometriotic lesion formation significantly suppressed with siRNA targeting NF-kappaB in comparison with the control group. CONCLUSIONS: The NF-kappaB pathway is involved in the development of endometriotic lesions in vitro, and NF-kappaB gene silencing reduces endometriotic angiogenesis and promotes cell apoptosis in the endometriotic lesions, suggesting that NF-kappaB might be a good target for endometriosis treatment.

[Small interfering RNA targeting NF-kappaB Inhibits human umbilical venous endothelial cells migration].

AIM: To investigate the effect of small interfering RNA(siRNA) targeting NF-kappaB on migration ability of human umbilical venous endothelial cells. METHODS: EAhy926 cells (Human umbilical vein endothelial cell line) were cultured with stimulation of vascular endothelial growth factor (VEGF), and then were transfected with NF-kappaB -siRNA (40 pmol/L) by using catiotic liposome lipofectamine(TM); 2000 as the transfecting agent. Cells transfected with negative control-siRNA (40 pmol/L), empty Liposome and nothing as control. Forty-eight hours later, cells were collected and prepared for RT-PCR, Western blot analysis, and determination of the migration inhibition rate. RESULTS: Compared with normal control group, both mRNA and protein levels of NF-kappaB were decreased obviously and at the same time cell migration inhibition rate was increased obviously in NF-kappaB-siRNA group. There were no significant differences between empty liposome group, negative control siRNA group and normal control group, respectively (P>0.05). CONCLUSION: Synthetic siRNA can effectively inhibit endothelial cell migration ability by means of blocking the signaling pathway of NF-kappaB. And siRNA targeting NF-kappaB may be useful for antiangiogenesis treatment.

[Construction of a recombinant adenoviral vector expressing human endostatin].

OBJECTIVE: To construct the recombinant adenovirus vector expressing human endostatin. METHODS: Human endostatin gene extracted from pGEM-T Easy vector containing the target gene fragment was successfully amplified using PCR and cloned into pShuttle2 vector. The target gene was subcloned into an adenovirus vector and the resulted recombinant adenovirus (Ad-hEndo) was linearized before transfected into HEK 293 packaging cells. The Ad-hEndo recombinant adenovirus was efficiently amplified in 293T cells and purified by CsCl density centrifugation, and the titer of the virus was determined. RESULTS: The amplified hEndostatin cDNA was verified by PCR and sequencing, and the resulted virus titer reached 5.2 x 10(9) pfu/ml. CONCLUSION: The recombinant adenovirus containing human endostatin gene has been successfully constructed, which may provide important basis for gene therapy research for angiogenesis-dependent diseases.

[Evaluation of tumor necrosis factor-alpha and tumor necrosis factor-beta in serum of patients with endometriosis].

OBJECTIVE: To evaluate the levels of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) before and after conservative laparoscopic surgery in patients with endometriosis. METHODS: The levels of TNF-alpha and TNF-beta in the serum of both 82 patients with EMS and 68 controls were determined by ELISA. RESULTS: The levels of TNF-alpha and TNF-beta in the serum of patients with EMS were significantly higher than those of the controls (P < 0.01), and they increased with the clinical terms ( P < 0.05). After clearance of endometrosis foci with laparoscopic conservative surgery, the TNF-alpha levels decreased significantly in EMS III - IV, and TNF-beta levels decreased significantly in EMS I - IV. CONCLUSION: Measuring TNF-alpha and TNF-beta levels in the serum of patients with EMS may have important value in postoperative follow-up, surveillance and evaluation of the effectiveness of the surgery.

[Expressions of nuclear factor-kappaB and intercellular adhesion molecule-1 in endometriosis].

OBJECTIVE: To investigate the association of nuclear factor-kappaB (NF-kappaB) and intercellular adhesion molecule-1 (ICAM-1) with endometriosis. METHODS: Immunohistochemistry was used to examine the NF-kappaB and VEGF protein expression in 35 specimens of normal endometrium, 48 eutopic endometrium of endometriosis and 76 ectopic endometrium, and the results were analyzed statistically. RESULTS: The expressions of NF-kappaB and ICAM-1 were found mainly in the glandular epithelial cells of the three endometrium specimens, with the ectopic endometriotic tissues showing the highest and normal endometrium the lowest expressions (P<0.001). NF-kappaB and ICAM-1 expressions were positively correlated to normal, eutopic and ectopic endometrium (r=0.688, 0.773 and 0.777, respectively, P<0.01). CONCLUSION: NF-kappaB and ICAM-1 may participate in the process of the pathogenesis in endometriosis.

[Clinical application of hysteroscopic electroresection in 775 cases].

OBJECTIVE: To review our experience with hysteroscopic electroresection in the treatment of uterine benign lesions. METHODS: We conducted a retrospective analysis of 775 cases of hysteroscopic surgery in view of the operation time, blood loss, complications and prognosis. RESULTS: The average operation time was 26.5+/-12.3 min and average blood loss 40.1+/-10.5 ml. The outpatients (n=539) were discharged 2 h after operation while the inpatients stayed for 2 or 3 d. Hyponatremia occurred in 1 case, and no death, uterine perforation or electric injury was recorded. During the follow-up for 3 months to 6 years, bleeding relapsed in 17 cases after transcervical resection of the endometrium, and the amenorrhea rate was 88.9%. The recurrence rate of endometrial polyp was 5.5% after electroresection of polyps. Menstruation as normal in all the cases after transcervical resection of the myoma. The uterine cavity became morphologically normal after transcervical resection of the septum without adhesions in the cavities. Improvement of menstruation was achieved in 55 cases (96.5%) after transcervical resection of the adhesion. A patient undergoing transcervical resection of the cervical lesion developed uterine and cervical adhesion 4 months later. CONCLUSIONS: For the patients with intrauterine benign diseases, hysteroscopic electroresection provides effective therapeutic options for lessening the invasive injury and decreasing the complications and blood loss.

[Expression of vascular endothelial growth factor and endostatin in peritoneal fluid of patients with endometriosis].

OBJECTIVE: To investigate the relationship of vascular endothelial growth factor (VEGF) and endostatin with endometriosis. METHODS: The levels of vascular endothelial growth factor and endostatin were measured using ELISA in 50 women with endometriosis (stage I-II26 cases and stage III-IV 24 cases) in comparison with 42 women without endometriosis. RESULTS: The VEGF, endostatin concentrations and VEGF/endostatin ratio in endometriosis group were significantly higher than the mean value in the control group (P<0.01). The VEGF and endostatin levels in stages III and IV were both significantly higher than those in stages I and II(397+/-81 pg/ml vs 315+/-64 pg/ml, 125+/-62 ng/ml vs 66+/-40 ng/ml, P<0.01). However, the VEGF/endostatin ratio was lower in the advanced stages. There was no significant difference between follicular phase and luteal phase except that the VEGF level in follicular phase was higher than that in luteal phases. CONCLUSIONS: Both VEGF and endostatin may play a role in the regulation of angiogenesis of endometriosis, and the balance of angiogenic stimulators and inhibitors may be critical to the development of endometriosis.