Research progress on the prevention and treatment of chemotherapy-induced ovarian damage. / åŒ–å­¦ç–—æ³•æ‰€è‡´åµå·¢æŸä¼¤çš„é˜²æ²»ç ”ç©¶è¿›å±•.

Chemotherapy is a main treatment option for malignant tumors, but it may cause various adverse effects, including dysfunction of female endocrine system and fertility. Chemotherapy-induced ovarian damage has been concerned with ovarian preservation but also the prevention and treatment of ovarian dysfunction. In this article, the mechanisms of ovarian injury caused by chemotherapy, including apoptosis of the follicle and supporting cells, follicle "burn out", ovarian stromal and microvascular damage; and influencing factors, including age at diagnosis, initial low pre-treatment anti-Müllerian hormone levels, toxicity, dose and regimen of chemotherapy drugs are reviewed based on the latest research results and clinical practice. The article also discusses measures and frontier therapies for the prevention and treatment of ovarian injury, including the application of gonadotropin releasing hormone agonists or antagonists, tyrosine kinase inhibitors, antioxidants, sphingosine-1-phosphate, ceramide-1-phosphate, mammalian target of rapamycin inhibitors, granulocyte-colony stimulating factor, stem cell therapy and artificial ovaries.

[Research advances on the role of exosomes in chemotherapy resistance of ovarian cancer].

Chemotherapy resistance is one of the biggest challenges in treatment of ovarian cancer. Mounting evidence shows that the exosomes shedding from tumor cells are considered to be involved in chemotherapy resistance of ovarian cancer by enhanced exosomal export of drugs, transferring RNAs or proteins and interfering with the bioactivity of therapeutic anti-tumor antibodies. In this review, we display the correlation between exosomes and chemotherapy resistance of ovarian cancer, the mechanism of exosomes involved in chemotherapy resistance of ovarian cancer, and discuss the potential clinical values of exosomes in chemotherapy resistance of ovarian cancer.

[Key anatomies of DeLancey's three levels of vaginal support theory: an observation in laparoscopic surgery].

OBJECTIVE: To observe and verify the key anatomies of DeLancey's three levels of vaginal support theory through laparoscopic surgery by space dissection technique. METHODS: The features and stress performance of related anatomies were observed and analyzed in laparoscopic type C hysterectomy and pelvic lymphadenectomy for cervical cancer by natural space exposures. RESULTS: The main ligament-like structure at level Ⅰ was the uterosacral ligament, which acted as the main apical fixation in the sacral direction, while the cardinal ligament was mainly composed of vascular system, lymph-vessels and loose connective tissue around them, lacking the tough connective tissue structures, which was connected to the internal iliac vascular system. There were no strong ligaments connected to the tendinous arch of pelvic fascia (ATFP) at the lateral side of vaginal wall at level Ⅱ. ATFP was the edge of the superior fascia of pelvic diaphragm, which was bounded by the fascia of the obturator. Its surface was smooth and close to the levator ani muscle and fuses with the vaginal fascia in about one thirds of middle lower segments of the vagina. When the ureter tunnel is separated, dense connective structures can be found in both anterior and posterior walls near the intersection of the ureter across uterine artery, fixing the bilateral angle of the bladder triangle, starting from the cervix and vagina and ending in the tunica muscularis vesicae urinariae. CONCLUSIONS: Based on the laparoscopic anatomy, the pelvic floor fascia ligament support above the levator ani muscle can be considered mainly around the vagina, and fascial ligament above the levator ani muscle can be simply considered as two parallel planes forming a "double hammock" structure, which may provide more anatomic data for pelvic floor reconstruction.

[Establishment of a prognostic model for preterm delivery in women after cervical conization].

OBJECTIVE: To establish a prognostic model for preterm birth in women after cervical conization, and to evaluate its effectiveness. METHODS: Seventy three women after cervical conization in Women's Hospital of Zhejiang University were included for this retrospective study. The influencing factors of preterm delivery were analyzed by Logistic regression analysis and a prognostic model was created. Receiver operating characteristic (ROC) curve was used for evaluation of the predictive ability of the model. Forty five women who underwent cervical conization were included for testing the validity of the model. RESULTS: For women after cervical conization, mother's age (OR=1.20, 95%CI:1.01-1.43, P<0.05) and cervical length during middle pregnancy (OR=0.06, 95%CI:0.01-0.21,P<0.01) were independent predictors for preterm birth. The regression model was Logit (P)=1.408-2.903×cervical length+0.186×age. The areas under the ROC curve (AUC) of the training dataset was 0.93 (95%CI:0.87-0.99). The sensitivity, specificity, Youden index, positive predictive value (PPV), negative predictive value (NPV) and accuracy with the cutoff value of -1.512 were 91.7%, 81.5%, 0.732, 68.8%, 95.7% and 84.5% respectively. The AUC of the testing dataset was 0.94 (95%CI:0.86-1.00). The sensitivity, specificity, Youden index, PPV, NPV and accuracy with the cutoff value of -0.099 were 92.9%, 90.3%, 0.832, 81.3%, 96.5% and 91.1%, respectively. CONCLUSIONS: The model based on the age and cervical length during middle pregnancy can effectively predict preterm delivery in pregnant women after cervical conization.

[Expression of miR-let-7e-3p in cervical intraepithelial neoplasm and cervix carcinoma and its clinical significance].

Objective: To investigate the expression of microRNA (miRNA, miR) let-7e-3p in different cervical lesions and its clinical significance. Methods: The expression of miR-let-7e-3p in the tissues of normal cervix (n=26), high-grade squamous intraepithelial lesion (HSIL) (n=37), and cervix carcinoma (n=101) were detected by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The correlation of miR-let-7e-3p expression with the clinicopathological parameters of patients with cervical cancer was analyzed. miR-let-7e-3p mimic was transfected into cervical carcinoma Siha cells. The cell cycle and apoptosis were determined by flow cytometry; cell proliferation was determined by CCK-8 kit; and the migration and invasion of cells were determined by Transwell assay. Results: The relative expression levels of miR-let-7e-3p in normal cervix, HSIL, and cervical carcinoma were 1.45±0.24, 0.79±0.05 and 0.46±0.04, respectively (all P<0.05). After transfection with miR-let-7e-3p mimic, the S-phase fraction and apoptosis rate of Siha cells were increased significantly compared with control group[(29.76±6.6)% vs (13.38±1.3)%, P<0.05; (5.98±1.38)% vs (3.53±0.79)%, P<0.05, respectively]. OD of transfected Siha cells at 48, 72 and 96 h were 0.57±0.11,0.65±0.04 and 0.84±0.14, which were significantly lower than those of untransfected Siha cells (0.74±0.05, 0.93±0.10 and 1.47±0.14, all P<0.05). The migration and invasion abilities of transfected Siha cells were not significantly changed (all P>0.05). Conclusion: The expression of miR-let-7e-3p is down-regulated in cervical neoplasms, which is associated with cell cycle arrest and proliferation inhibition of cervical cancer cells.

[Clinical significance of HPV L1 capsid protein detection in cervical exfoliated cells in high-risk HPV positive women].

OBJECTIVE: To explore the clinical significance of human papillomavirus L1 capsid protein detection in cervical exfoliated cells in high-risk HPV positive women. METHODS: From November 2012 to June 2013, 386 high-risk HPV positive (detected by hybrid capture II) cases were enrolled as eligible women from Huzhou Maternity & Child Care Hospital and Women's Hospital, School of Medicine, Zhejiang University. All eligible women underwent liquid-based cytology (ThinPrep) followed by colposcopy. Biopsies were taken if indicated. Cervical exfoliated cells were collected for HPV L1 capsid protein detection by immunocytochemistry. Expression of HPV L1 capsid protein in groups with different histological diagnosis were compared, and the role of HPV L1 capsid protein detection in cervical exfoliated cells in cervical lesions screening was accessed. RESULTS: Total 386 enrolled eligible women were finally diagnosed histologically as follwed: 162 normal cervix, 94 low-grade squamous intraepithelial lesion (LSIL), 128 high-grade squamous intraepithelial lesion (HSIL) and 2 squamous cervical cancer (SCC). The positive expression rate of HPV L1 in HSIL+ (HSIL or worse) group was significantly lower than that in LSIL- (LSIL or better) group (19.2% vs 66.4%, P=0.000). While identifying HSIL+ in HPV positive cases and compared with cytology, HPV L1 detection resulted in significant higher sensitivity (80.77% vs 50.77%, P=0.000) and negative predictive value (NPV; 87.18% vs 76.47%, P=0.004), significant lower specificity (66.41% vs 81.25%, P=0.000), and comparable positive predictive value (PPV; 54.97% vs 57.89%, P=0.619). To identify HSIL+ in HPV-positive/cytology-negative women, the sensitivity, specificity, PPV, and NPV of HPV L1 detection were 87.50%, 61.54%, 41.18%, and 94.12% respectively, while 80.00%, 86.36%, 80.00% and 86.36% respectively in HPV-positive/atypical squamous cell of undetermined significance (ASCUS) women. CONCLUSIONS: HPV L1 capsid detection in cervical exfoliated cells have a role in cervical lesions screening in high-risk HPV positive women, and may be a promising triage for high-risk HPV-positive/cytology-negative or ASCUS women.