Clinical characteristics and prognostic characterization of endometrial carcinoma: a comparative analysis of molecular typing protocols.

BACKGROUND: Endometrial carcinoma (EC) is one of the most common gynecological malignancies in China and globally, accounting for the fourth-prevalent cancer in women. Although numerous studies have confirmed prognostic value of The Cancer Genome Atlas (TCGA) molecular subgroups, it is unclear how they are combined with histological features. The main objective of this study was to compare ProMisE and TCGA classification for the rapid and accurate prediction of prognosis within EC patients, together with the provision of a revised strategy for individualized diagnosis and treatment of patients. METHODS: Within this study, 70 patients with EC from Beijing Tsinghua Changgeng Hospital (affiliated to Tsinghua University) were retrospectively examined between July 2015 and December 2021. Samples were processed for determination of clinical markers, together with ProMisE and TCGA classification. RESULTS: Comparative analysis across four TCGA types (POLE, Low-CN, High-CN, and MSI-H) and age, was statistically significant (χ²= 7.000, p = 0.029). There was no significant difference observed among the four TCGA types and FIGO stage, vascular invasion and depth of invasion, or lymph node metastasis and tumor area. There was no significant association between the expression of Vimentin, Ki-67, PTEN, MSH2, PAX-8, ß-catenin, CD10, ER, PR, P16, MLH1, and PMS2 with the four TCGA types. In addition, p63 expression (χ²= 11.09, p = 0.029) and p53 expression (χ²= 11.585, p = 0.005) were statistically significant. Numerous models demonstrated that patients with POLE mutations and low-CN had higher progression free survival (PFS) and overall survival (OS), whereas those with high-CN had lowest values. The log-rank test revealed that the survival rate of PR-positive and ER-positive patients was significantly higher (p < 0.001). CONCLUSION: Overall, these results can be of additional benefit for clinical applications, in comparison to the ProMisE classification method. In addition, PR, ER, vascular infiltration, hyperlipidemia and atherosclerosis were found to be the key factors affecting EC prognosis.

Biofilms of vaginal Lactobacillus in vitro test.

This paper focuses on biofilms of Lactobacillus spp. - a type of normal flora isolated from healthy human vaginas of women of childbearing age; thereupon, it broadens the research scope of investigation of vaginal normal flora. The static slide culture method was adopted to foster biofilms, marked by specific fluorescence staining. Laser scanning confocal and scanning electron microscopy were used to observe the microstructure of the biofilms. Photographs taken from the microstructure were analysed to calculate the density of the biofilms. The body of Lactobacillus spp., though red, turned yellow when interacting with the green extracellular polysaccharides. The structure of the biofilm and aquaporin within the biofilm were imaged. Lactobacillus density increases over time. This study provides convincing evidence that Lactobacillus can form biofilms and grow over time in vitro. This finding establishes an important and necessary condition for selecting proper strains for the pharmaceutics of vaginal ecology.

[Confocal laser scanning electron microscopy for assessment of vaginal Lactobacillus crispatus biofilm].

OBJECTIVE: To investigate the female vaginal Lactobacillus crispatus biofilm by using confocal laser scanning microscopy (CLSM),thus revealing the formation of biofilm. METHODS: The cover slide biofilm culture approach in vitro was employed for induction of the vaginal Lactobacillus crispatus biofilm formation. Following the culture for 2, 4, 8, 12, 16, 20, 24, 48, 72, 96 and 120 hours, the cover slide was removed for subsequent staining with the fluoresce in isothiocyanate-conjugated concanavalin A(FITC-ConA) and propidium (PI).This was followed by determination of the formation and characteristics of the vaginal Lactobacillus crispatus biofilm by using CLSM. RESULTS: The CLSM images of biofilm formation at different time points were captured, suggesting that the vaginal Lactobacillus crispatus adhesion occurred at h 4, which was in reversible attachment, then more and more Lactobacillus crispatus aggregated at h 8 to h 20, which was in irreversible attachment.Lactobacillus crispatus clustered at h 20, with early development of biofilm architecture.Then the biofilm with extracellular matrix around the bacteria was set up at h 24,with gradual matureation at h 24 to h 48.The biofilm dispersed at h 72. The biofilm density of cultivating for 20 hours was 42.7 × 10⁻³ ± 6.8 × 10⁻³ ,and for 24 hours increased to 102.5 × 10⁻³ ± 23.1 × 10⁻³, suggesting a significant difference, P<0.05. This meant that mature biofilm was formed at h 24. CONCLUSION: The vaginal Lactobacillus crispatus is able to form typical biofilm with distinct developmental phases and architecture characteristics.Mature biofilm is formed at h 24 to h 48, then the biofilm begins to disperse.

[Sucrose gel for treatment of bacterial vaginosis: a randomized, double-blind, multi-center, parallel-group, phase III clinical trial].

OBJECTIVE: To evaluate the cure effectiveness and safety of sucrose gel in the treatment of bacterial vaginosis through a multi-center, randomized, double-blind, parallel controlled clinical study. METHODS: A clinical research method of multi-center, randomly double-blind, and dose group parallel comparison was adopted. In the study, 533 patients with bacterial vaginosis were randomly divided into two groups, which included 214 cases in the control group (5.0 g metronidazole gel) and 319 cases in the trial group (5.0 g sucrose gel ). The patients were treated with different medication according to the group where they were. All the cases in these two groups were treated with drugs vaginally twice in a day, morning and evening separately, for 5 days. The curative effect and safety evaluation were assessed from 7 to 10 days and 21 to 30 days after treatment respectively. RESULTS: The efficacy of the comprehensive clinical treatment showed that the cure rate of metronidazole gel group and sucrose gel group were 70.53% and 80.83% respectively 7 to 10 days after treatment. The recovery rate of Nugent score for vaginal smear were 71.50% and 81.15% respectively. The differences in the efficacy between these two groups were significant statistically (P<0.05). However, the cure rates of metronidazole gel group and sucrose gel group were 63.29% and 61.98% respectively 21 to 30 days after treatment. No statistically significant difference (P>0.05) could be found in the cure rates of the two groups. CONCLUSION: The clinical comprehensive efficacy and recovery of vaginal bacteria of sucrose gel group in the treatment of bacterial vaginosis were obviously superior to those of metronidazole gel 7 to 10 days after treatment. The susucrose gel could improve the clinical efficacy index and laboratory index of bacterial vaginosis. Other effects included the release of clinical symptoms, and the recovery of the normal micro-environment in the vagina according to the Nugent score. The curative efficacy of sucrose gel was equal to that of metronidazole gel 21 to 30 days after treatment. In the future, sucrose gel treatment can be a new strategy for the treatment of bacterial vaginosis. Various advantages can be taken to improve the cure rate of bacterial vaginosis and reduce the shortcomings produced by this disease.

[Efficacy of postoperative simple chemotherapy and concurrent chemoradiotherapy in FIGO stage IB2-IIB cervical cancer].

OBJECTIVE: To evaluate the effectiveness of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for stage IB2-IIB cervical cancer. METHODS: Seventy-nine patients with stage IB2-IIB cervical cancer were treated with NAC followed by radical hysterectomy. According to different adjuvant therapies, patients were divided into postoperative chemotherapy group (47 cases) and postoperative radiotherapy/concurrent chemoradiotherapy group (32 cases). Regimens for NAC and postoperative chemotherapy were BIP (bleomycin+ ifosfamide+ cisplatin/carboplatin) or TP (paclitaxel+ cisplatin/carboplatin). An average of 1.1±0.3 cycles of NAC and 3.4±1.2 cycles of postoperative chemotherapy were prescribed. RESULTS: Toxicities due to chemotherapy were generally tolerable. Overall response rate of NAC was 88.6%. With a median follow-up period of 42 months, the three-year progression-free survival rates of the two groups were 88.5% and 84.3%, the total survival rates were 90.3% and 86.4%, respectively. There was no statistically significant difference. The recurrent rates were 10.6% and 21.8% in the two groups. In the absence of radiotherapy, pelvic recurrence was observed in two patients; the other three had distant metastases. CONCLUSION: The results indicate that NAC followed by surgery plus postoperative chemotherapy but no radiotherapy offers a viable option in the treatment of stage IB2-IIB cervical cancer. The patients can tolerate the side effects of chemotherapy with better efficacy.

[Results of different postoperative adjuvant therapies for stage Ib-IIa cervical carcinoma with risk factors].

OBJECTIVE: To investigate the effects of postoperative adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) or radiotherapy(RT) for Ib-IIa cervical cancer with risk factors. METHODS: From March 1995 to June 2010, there were 137 patients underwent radical hysterectomy and systematic pelvic lymphadenectomy for stage Ib-IIa cervical cancer admitted at Peking University First Hospital. These patients had risk factors, intermediate risk factors including bulky tumor ( > 4 cm) , lymph vascular space invasion, deep stromal invasion; high risk factors including positive surgical margin, parametrial invasion, lymph node involvement. Of the all patients, 79 cases of them were treated with CT, 58 of them were treated with RT or CRT. The 5-year survival and prognosis factors were analyzed retrospectively, the prognosis was compared between two adjuvant therapy groups. RESULTS: The univariate analysis shown that types of pathology, different grade of risk factors, stroma invasion and lymph node involvement were prognostic factors of 5-year overall survival. Patients with squamous cell carcinoma, intermediate risk factors, no parametrial invasion, and no lymph node involvement had better prognosis(P < 0.05). Whether patients with high-risk factors or intermediate-risk factors, the 5-year overall survival and 3-year disease-free survival had no difference between CT and RCT or RT groups respectively. Cox regression multivariate analysis of survival indicated that clinical stages, types of histology, different grade of risk factors were independent prognostic indicator. Patients with early stage, squamous cell carcinoma, intermediate risk factors had better prognosis. Univariate and multivariate analysis indicated that different postoperative adjuvant therapies had no effects on the prognosis. The 5-year overall survival was 88.6% in patients treated with CT, and 89.7% in patients treated with RT or CRT (P = 0.455) . CONCLUSION: There are equivalent therapeutic results between CT and RT or CRT for patients with risk factors after radical surgery, CT may be as one choice of postoperative adjuvant therapy for stage Ib-IIa cervical carcinoma with risk factors.

[Screening and sampling of endometrial carcinoma accuracy of the endometrial cytology test for the screening of endometrial cancer].

OBJECTIVE: To evaluate the accuracy of endometrial cytology test (ECT) for the diagnosis of endometrial cancer or precancerous lesions and then discuss the value of ECT as a screening tool for endometrial cancer.Secondly, to investigate related characteristics and independent risk factors of epidemiology of endometrial carcinomas and atypical endometrial hyperplasia to advise proper crowd for endometrial carcinomas screening and monitoring. METHODS: Totally 1717 preoperative questionnaires on hysteroscopy + dilation & curettage, histopathology and endometrial cytological tests in Peking University First Hospital, People's Hospital of Beijing Daxing District and Beijing Cancer Hospital, from March 2009 to May 2013 were completed. Histopathologic diagnoses were used as the gold standard for determining the accuracy of ECT.Extrapolation: applied binary logistic regression method to narrow down the risk factors of histopathology and endometrial cytological examination. RESULTS: Satisfaction rate of cytological specimens and pathological specimens were 96.45% (1656/1717) and 91.44% (1570/1717), respectively. ECT provided sufficient material for the diagnosis significantly more often than histopathology (P < 0.05). For the ECT diagnosis of endometrial cancer: accuracy was estimated at 88.2%, sensitivity at 87.3%, specificity at 88.3%, positive predictive value (PPV) at 41.9%, negative predictive value (NPV)at 98.6%.Univariate analysis revealed that risk factors of diagnosis of endometrial carcinomas and atypical hyperplasia of histopathology were included:body mass index (BMI) ≥ 25 kg/m(2), age ≥ 40 years old, diabetes mellitus, hypertension, menopause, family history of malignant tumor (all P < 0.10). Multifactor analysis revealed that the independent risk factors were included:BMI ≥ 25 kg/m(2), age ≥ 40 years, menopause and family history of malignant tumor (all P < 0.05). CONCLUSIONS: The results of the current study indicated that the accuracy of ECT for the diagnosis of endometrial cancer was high.Furthermore, ECT could be a useful tool for the screening of endometrial cancer.Independent risk factors of endometrial carcinomas and atypical endometrial hyperplasia including:age over 40 years, BMI ≥ 25 kg/m(2), menopause and family history of malignant tumor.

5-aza-2'-deoxycytidine improves the sensitivity of endometrial cancer cells to progesterone therapy.

OBJECTIVE: Progesterone has been proven to have limited effects on endometrial cancers (ECs), mainly owing to the down-regulation of progesterone receptor (PR). Here, we explored whether 5-aza-2'-deoxycytidine (5-aza-CdR), a demethylating agent, could enhance the susceptibility of EC cells to medroxyprogesterone acetate (MPA). METHODS: Ishikawa and KLE cell lines were treated with 5-aza-CdR and/or MPA. The expression of PR, PR target genes, and matrix metalloproteinase (MMP) was investigated by real-time polymerase chain reaction and Western blot. Promoter methylation was detected by methylation-specific polymerase chain reaction. The effects of 5-aza-CdR and/or MPA on cell proliferation, apoptosis, and invasion of EC cells were evaluated by 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium assay, flow cytometry, invasion assay, and gelatin zymography, respectively. RESULTS: 5-Aza-2'-deoxycytidine significantly increased the expression of PR and its downstream targets by demethylating PR promoter in both Ishikawa and KLE cells. 5-Aza-2'-deoxycytidine combined with MPA synergistically suppressed the EC cell growth by inducing cell cycle arrest at G2/M phase and apoptosis. Furthermore, 5-aza-CdR synergized with MPA to inhibit the invasion of EC cells, perhaps owing to the down-regulation of MMP-2 and MMP-9 expression and activity. CONCLUSIONS: 5-Aza-2'-deoxycytidine and MPA synergistically inhibit EC cell growth and invasion. Their combined use may provide a new effective therapeutic opportunity for endometrial carcinoma.

[Methylation of matrix metalloproteinases-2 promoter in endometrial cancer invasion].

OBJECTIVE: To investigate the regulation of DNA methylation on the expression of MMP-2 gene, and the effect of 5-aza-2'-deoxycytidine (5-aza-CdR) on invasiveness of endometrial cancer cells. METHODS: Human endometrial cancer cell lines Ishikawa and HEC-1A were treated with 5-aza-CdR. After genomic DNA was extracted from the cells and treated with bisulfate sodium, clone sequencing was used to detect methylation of the matrix metalloproteinases-2 (MMP-2) promoter region. Ishikawa and HEC-1A cells were treated with different concentrations of 5-aza-CdR, and the effect on the invasion and metastasis to the endometrial cancer (EC) cells were detected by Transwell invasion chamber. The MMP-2 mRNA expression was detected by real-time quantitative PCR. RESULTS: Although the MMP-2 promoter showed global hypomethylation status, the methylation of CG dinucleotide sites located on the transcription factor binding sites had high positive frequencies, which were 80% and 70% in HEC-1A cells and 60% and 40% in Ishikawa cells, respectively. The methylation frequencies reduced to 20% and 10% in HEC-1A cells by demethylating agent 5-aza-CdR and the CG sites in Ishikawa cells were totally demethylated. Moreover, after 72 h of treatment with different concentrations of 5-aza-CdR, the expression of the MMP-2 mRNA and transmembrane number of both Ishikawa and HEC-1A cells were significantly upregulated compared with the control group (P<0.05). CONCLUSION: Methylation of CG dinucleotide sites of the MMP-2 promotor region may be associated with the regulation of gene transcription. The 5-aza-CdR can promote the invasion and metastasis of endometrial cancer cells in vitro by upregulating the MMP-2 mRNA expression.

[Analysis of diversity of vaginal microbiota in healthy Chinese women by using DNA-fingerprinting].

OBJECTIVE: To analyze the diversity of healthy women's vaginal dominant flora in different physiological states with PCR-denaturing gradient gel electrophoresis (PCR-DGGE), to establish the basis for the future study of lower genital tract infections, and to provide a theoretical basis for the development of vaginal probiotics adapted to Chinese females. METHODS: Women who underwent routine gynecologic examinations in Peking University First Hospital from October 2009 to January 2010 were enrolled, including 30 at reproductive age and 30 at post menopause age. Vaginal samples were collected and then total bacterial DNA was extracted. Universal bacterial primers were used to amplify the V3 region of 16S rDNA gene. PCR products were analyzed by denatured gradient gel electrophoresis (DGGE). Featured bands on DGGE were recovered, cloned and sequenced. Alignment with known sequence was made by using Blast on GenBank to identify bacterial strains so as to analyze the diversity of healthy women's vaginal dominant flora in different physiological states. RESULTS: (1) Vaginal flora in healthy Chinese women at their reproductive age were relatively simple, Lactobacillus were the dominant bacteria. Common bacteria included: Lactobacillus crispatus, Lactobacillus iners,and Lactobacillus gasseri. While L. iners were the dominant vaginal bacteria that could not be recognized by traditional method. (2) Vaginal bacteria in the women at post menopause age were more complex than in those at reproductive age. Common bacteria included: Lactobacillus iners, Lactobacillus crispatus, Escherichia coli, Streptococcus agalactiae, Streptococcus gallolyticus, Veillonella sp., Streptococcus intermedius, Streptococcus anginosus, Prevotella sp., Anaerococcus lactolyticus and Bacteroides fragilis. CONCLUSION: Based on the DGGE analysis, the most common vaginal bacteria in Chinese healthy women at reproductive age are Lactobacillus crispatus, Lactobacillus iners,and Lactobacillus gasseri. the most common vaginal bacteria in healthy post-menopausal women are Lactobacillus iners, Lactobacillus crispatus, Escherichia coli, Streptococcus sp., Prevotella sp.,Bacteroides fragilis and lactic acid producing Veillonella sp. and Anaerococcus lactolyticus. Meanwhile Lactobacillus iners was firstly found by DGGE to be the dominant vaginal bacteria in different physiological states.

[Effect of Ras signal regulating Cox7a2 expression and its sub-cellular location in testicular interstitial cell].

OBJECTIVE: To investigate the co-sub-cellular-location of Cox7a2 and Ras. METHODS: Ras and its mutant plasmid were cloned by RT-PCR and sequence analysis. Cox7a2-pEYFP-N1, Ras-pEYFP-N1 and N17-Ras-pEYFP-N1 fluorescent protein vectors were constructed and transfected into TM3 cells. RESULTS: Cox7a2 was located in the mitochondria, but its location was changed by the expression of Ras. When the dominant negative ras was expressed in the cells, the Cox7a2 located into the mitochondria again. CONCLUSION: Cox7a2 mediated testosterone production, which might be at least in part related with the Ras signaling pathway. Ras may be the regulating target and further investigation is needed to make it clear.

[Testicular sperm cryopreservation for male fertility preservation].

OBJECTIVE: To investigate the effectiveness of testicular sperm cryopreservation in male fertility preservation by evaluating the clinical outcome of ICSI cycles with frozen-thawed testicular sperm for azoospermia patients. METHODS: We retrospectively analyzed 96 samples of cryopreserved testicular sperm obtained by testicular biopsy, vasovasostomy (V-V), vasoepididymostomy (V-E) , of which 55 were subjected to 60 ICSI cycles with frozen-thawed testicular sperm. We evaluated the rates of sperm recovery, fertilization, cleavage, transferable and good-quality embryos, clinical pregnancy, pregnancy outcome, and health of the newborns. RESULTS: All the frozen testicular sperm samples were recovered successfully. The rates of fertilization, 2PN fertilization, cleavage, available embryos and good-quality embryos were 77.6, 69.4, 99.4, 84.5 and 40.8%, respectively. There were transferable embryos in all cycles. Fresh embryos were transferred in 52 of the 60 cycles, with the clinical pregnancy rate of 57.7% (30/52), including 19 singletons and 11 twins, and the rates of implantation and miscarriage were 38.7% (41/106) and 3.33% (1/30). Up to the present time, there have been 20 healthy newborns, including 12 boys and 8 girls, and another 13 ongoing pregnancies. No birth defects have been found so far. CONCLUSION: Desirable clinical outcomes can be obtained from ICSI cycles with frozen-thawed testicular sperm, and testicular sperm cryopreservation is an effective method of fertility preservation for azoospermia males.

Second primary malignancies after ovarian cancer: A SEER-based analysis (1975-2016).

OBJECTIVE: To investigate the risk of occurrence of second primary malignancies (SPMs) in survivors of ovarian cancer (OC) using large data from the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Multiple primaries standardized incidence ratios (MP-SIRs) to calculate the risk of developing second primary malignancies after a diagnosis of ovarian cancer. RESULTS: Of our included 59,880 women with OC, 3972 cases (6.6%) developed 4495 s primary malignancies over an average follow-up period of 114.39 (±102.66) months. Overall, the risk of occurrence of second primary malignancies after a diagnosis of OC was greater than what would be expected for a reference US population (SIR = 1.05, 95%CI = 1.02-1.08, p-value < 0.05). The occurrence of second myeloid malignancies and second thyroid cancer were most notable across our latency periods. Among the most significant second primary malignancies by latency were malignancies of the appendix (SIR = 14.04, 95%CI = 5.65-28.93, p-value <0.05) at 2-11 months, the small intestine (SIR = 3.15, 95%CI = 1.76-5.2, p-value <0.05) at 12-59 months, and the urinary bladder (SIR = 1.63, 95%CI = 1.3-2.02, p-value <0.05) after 10 years of an OC diagnosis. CONCLUSION: Women with OC are at significant risk for the development of second primary malignancies across all sites, as compared to a reference US population, and may benefit from second primary malignancies site-specific screening post-diagnosis.

[Significance of phosphoinositide 3 kinase/AKT pathway alterations in endometrial carcinoma].

OBJECTIVE: To investigate the clinicopathologic and prognostic implications of phosphoinositide 3 kinase (PI3K)/AKT pathway alterations in endometrial cancers of Chinese women. METHODS: The expression of PTEN, p-AKT, and ER/PR was assessed in 71 cases of endometrial carcinoma by immunohistochemistry (EnVision method). The PIK3CA mutation at exon 9 and exon 20 was analyzed by PCR and direct sequencing in 34 tumors. RESULTS: (1) Of the 71 cases of endometrial carcinoma, 65 cases were endometrioid adenocarcinoma (EEC) and 6 cases were nonendometrioid adenocarcinoma (NEEC). PTEN loss of expression was found in 63.4% (45/71) of tumors, and more commonly occurred in EEC (66.2%, 43/65) than that in NEEC (2/6, P = 0.18). Patients with PTEN loss in their tumors (45 cases) had a better survival than those without (26 cases, P = 0.07). In ER negative subgroup, the patients with PTEN loss of expression (12 cases) had longer survival than those with normal PTEN expression (7 cases; P = 0.04). (2) The frequency of PIK3CA mutation was 41.2% (14/34) with a hot mutation spot at T544 in exon 9. PIK3CA mutations more commonly occurred in EEC (44.8%, 13/29) than in NEEC (1/5, P > 0.05). The mutations at exon 9 more commonly occurred in EEC, well- and moderately-differentiated EEC, and tumors at early stage (P > 0.05). On the contrary, in tumors at early stages, the frequency of mutations in exon 20 (14.3%, 4/28) was significantly lower than that at late stages (4/6, P = 0.01). (3) p-AKT was positive in 59.2% (42/71) of tumors that were more frequently found in EEC (60.0%, 39/65) than that in NEEC (3/6, P = 0.68). However, the significant difference of p-AKT expression was found between well- and moderately-differentiated EEC (75.0%, 21/28; 53.6%, 15/28) and poorly-differentiated EEC (3/9, P = 0.02). Moreover, p-AKT expression was significantly correlated with positive ER (r = 0.339, P = 0.00). CONCLUSIONS: Endometrial carcinoma patients with loss of PTEN and p-AKT positivity have a favorable prognosis. PIK3CA mutations at exon 9 or 20 may have different impact on the prognosis. The function of PTEN loss and p-AKT expression may vary according to different hormone status.

Screening and identification of Lynch syndrome: a systematic review of the frequency of Lynch syndrome-associated clinicopathologic and molecular characteristics in Lynch syndrome gynecologic cancers.

BACKGROUND: This study aimed to investigate the frequency of Lynch syndrome-associated clinicopathologic and molecular characteristics in Lynch syndrome gynecologic cancers. METHODS: A systematic literature search was conducted in the literature databases (Medline, CINAHL, EMBASE, Google Scholar, Cochrane Library, and Clinicaltrials.gov) to identify the studies describing clinicopathologic characteristics, MMR protein immunohistochemistry and/or MSI, MLH1 methylation, and genetic testing in Lynch syndrome gynecologic cancer patients. RESULTS: A total of 24 of the evaluated studies that met the inclusion criteria were identified. A clinicopathological examination confirmed 242 endometrial cancer, 17 clear cells endometrial cancer, 35 serous endometrial cancer, 30 mixed and 21 other endometrial cancer. Thus, a total of 345 endometrial cancer was confirmed from the screening of 1,317 gynaecological cancer. However, the morphological analysis demonstrated 236 patients with endometrial cancer associated with Lynch syndrome. The frequency of confirmed LS with endometrial cancer was 68.40%. At diagnosis, the median age was 49.94±4.34 years, and the average BMI was 26.07±3.77 kg/m2. Endometrioid histology and stage I disease were the most frequent at 70.97% and 71.19% histological type and FIGO stage, respectively. Similarly, morphological and histological analysis demonstrated a higher degree of grade I cancer (47.28) and lymphovascular invasion (56.52%), respectively. DISCUSSION: Lynch syndrome-associated clinicopathologic and molecular characteristics occur significantly in Lynch syndrome gynecologic cancers and may improve risk stratification and triaging of gynecologic cancers for genetic testing.

[Clinical analysis for death in gynecological patients].

OBJECTIVE: To discuss the death affairs of gynecological patients and find the measurements of down-regulating the mortality. METHODS: We conducted a retrospective study on the 54 death in-patients in our gynecological department during January 1993 and June 2008. Associated with literature, the data were analyzed according to primary diseases, death causes and clinical demonstrations, in order to probe into the rule of death in gynecological in-patients. RESULTS: The main death causes were gynecological cancers, such as ovarian carcinoma, cervical carcinoma, choriocarcinoma, invasive mole and endometrial carcinoma, which accounted for 79.6 percent (43/54) of gynecological death. Sudden death took up 24 percent (13/54), with death causes of cardio-cerebral vascular events, such as myocardium infarction, pneumonia embolism and cerebral embolism. CONCLUSION: Gynecological oncology is still the main disease threatening women's lives. Emphasis should be put on the physical and surgical complications of the patients. We should attach more importance to the observation and associated treatment of post-operative and post-chemotherapeutic patients with high risks.

[Sucrose Gel for the treatment of bacterial vaginosis: a phase II clinical trial].

OBJECTIVE: To evaluate the effective dose and safety of S-Gel in the treatment of bacterial vaginosis. METHODS: Clinical research method of multi- center, randomly double-blind, and dose group parallel comparison was adopted. In the study, 96 bacterial vaginosis patients were randomized into three groups: Group A, S-Gel 5.0 g, 32 patients; Group B, S-Gel 7.5 g, 32 patients; Group C, placebo, 32 patients. The patients were treated with different methods. Safety and efficacy were analyzed 3 to 4 days and 8 days after the treatment, respectively. RESULTS: The efficacy of comprehensive clinical treatment showed that: 8 days after the treatment, the cure rates of group A (5.0 g), group B (7.5 g), and group C (placebo) were 84.38%, 86.67%, and 3.13% respectively. No difference of statistic significance was found in groups A and B, difference of statistical significance was found in group A and group C, group B and group C respectively (P<0.001). CONCLUSION: As compared with placebo, S-Gel 7.5 g and 5.0 g bid (in the morning and evening) could obviously improve the clinical efficacy index and laboratory index of bacterial vaginosis. Other effects included the release of clinical symptoms, and the recovery of the normal micro-environment in the vagina. No significant difference was found in the cure rates of the two dose groups.

[Multicenter randomized, double-blind, placebo-controlled trial of prostaglandin E1 cream for female sexual arousal disorder].

OBJECTIVE: To investigate the efficacy and safety of alprostadil cream in management of female sexual arouse disorder (FSAD), and its appropriate dose for clinical prescription. METHODS: The volunteers were assigned randomly to four groups which received alprostadil cream in different dosage (500 µg, 700 µg and 900 µg) or placebo cream, respectively. The cream was applied to the clitoris and G-spot before coitus. The efficacy was assessed by comparing the satisfactory rate of sexual arousal, the score of female sexual function index (FSFI) and female sex disorder scale (FSDS) and the general appraised question (GAQ) before and after the treatment. The safety was evaluated by the adverse effects that appeared including symptoms, physical and biochemical examination. RESULTS: Totally, 400 women enrolled in this study with 374 assigned to the group for efficacy evaluation and 387 cases to the group for safety analysis. No significant difference was found among the four groups in the demographic characters and sexual baseline. The increase of satisfactory percentage of sexual arousal in the four groups (placebo, 500 µg, 700 µg and 900 µg) was 22.63%, 36.67%, 34.01%, and 44.29%, respectively (P<0.05), and the increase was statistically higher in the 900 µg group than in the placebo group (P<0.0167). The elevated FSFI score above the baseline in the treatment groups (900 µg 22.89, 700 µg 21.69, and 500 µg 20.71) were higher than that in the placebo group (14.68, P<0.05), while the reduced FSDS score below the baseline (900 µg 25.97, 700 µg 21.98, and 500 µg 20.27) were higher than that of the placebo (17.60, P<0.05). No significant difference was found in the four groups in GAQ (P=0.054). The main common adverse effect was topical stimulation. No adverse effect was reported in physical and biochemical examination, electrocardiogram (ECG) or Thinprep cytologic test (TCT). CONCLUSION: Alprostadil cream can treat female sexual arousal disorder effectively with the maximum effect at the dose of 900 µg and without significant adverse effect except for mild topical stimulation.

[Expression of Notch3 and Notch intracellular domain in ovarian carcinoma and effect of N-[N-(3,5-difluorophenyl) acetyl-L-alanyl]-S-phenyl glycine t-butyl ester on ovarian carcinoma cell].

OBJECTIVE: To study the expression and clinical significance of Notch3 and Notch intracellular domain (NICD) in ovarian carcinoma and the effects of N-[N-(3,5-difluorophenyl) acetyl-L-alanyl]-S-phenyl glycine t-butyl ester (DAPT), a γ-secretase inhibitor on the proliferation and apoptosis in OVCAR3, A2780 ovarian carcinoma cell lines. METHODS: Western blot was used to detect the expression of NICD in the tissues from 58 ovarian carcinomas patients and 21 normal ovarie, who were admitted in Peking University First Hospital from July 2006 to June 2009.Immunohistochemistry was also used to detect the expression of Notch3 in these tissues. The relationship with clinical features of ovarian carcinoma was also analyzed. Proliferation of OVCAR3 and A2780 ovarian cancer cells was determined by methyl thiazolyl tetrazolium (MTT) assay, cell cycles and apoptosis and index of proliferation were detected by flow cytometry method. The expression of NICD in OVCAR3 and A2780 cells incubated with DAPT was detected by western blot. RESULTS: (1) The expression level of NICD in ovarian carcinomas was significantly higher than that in normal ovarian tissues (1.64 ± 0.19 vs. 0.98 ± 0.20; P < 0.05). The NICD expression was higher in ovarian cancers with low grade or advanced stage than those in high-middle grade or early stage, respectively (1.90 ± 0.22 vs. 1.25 ± 0.21, 1.80 ± 0.21 vs. 1.21 ± 0.15; all P < 0.05). The Notch3 protein was stained positively in cytoplasm, nuclear and cell membrane. The expression of Notch3 was higher in ovarian carcinomas than that in normal ovaries [78% (45/58) vs. 24% (5/21); P < 0.01]. While, there were no stasistical difference in different pathological types, stages, differentiation of ovarian carcinoma. There was no difference between the patients with adjuvant chemotherapy or not. (2) After OVCAR3 and A2780 cells incubated with DAPT 24, 48, 72 hours, NICD expression was significantly lower than that in control group (P < 0.05). The effects of DAPT inhibited the proliferation and prompted the apoptosis of OVCAR3 and A2780 cells were depended on the concentrations and times. CONCLUSIONS: Notch3 and NICD may play a key role in the occurrence and progress of ovarian carcinoma. The mechanism of DAPT inhibited the proliferation and prompted the apoptosis of OVCAR3 and A2780 cells may be due to decreased the formation of NICD.

Vaginal microbiome analysis of healthy women during different periods of gestation.

To assess the vaginal microbiome throughout full-term uncomplicated pregnancy, a longitudinal study was designed for 12 healthy women who had prepared to become pregnant and then delivered at term (38-42 weeks) without complications. The vaginal microbial community was studied at pre-pregnancy, 8-12, 24-28, 37-38 weeks of gestation, and puerperium, using hypervariable tag sequencing of the V3-V4 region of the 16S rRNA gene. Sequencing produced approximately 10 million reads on the Illumina MiSeq. Members of the Firmicutes phyla were prevailing before and during pregnancy periods, and the proportion was quite as Proteobacteria until puerperium. Lactobacillus genus was abundant before and during pregnancy, but post-delivery vaginal microflora variety turned diverse. The species-level analysis revealed that a healthy vaginal microbiome before or during pregnancy was prominently dominated by Lactobacillus crispatus. Furthermore, PCoA analysis revealed for differences in the bacterial community composition between the two levels of Lactobacillus species in pre-pregnancy and pregnancy period (PC1 contribution of 58.46%, PC3 contribution of 8.64%). Based on the taxonomic and PCoA analysis, we found that L. crispatus was dominant in the vaginal microflora of healthy women before or during pregnancy, but at the puerperium, the status changed leading to decreased abundance of protective Lactobacillus species that made vaginal micro-ecological barrier vulnerable to diseases. Additionally, vaginal pH was an important environmental property affecting the vaginal microbial community.