A multicenter, randomized, open and positive parallel controlled clinical study of clotrimazole vaginal expansion suppository and vaginal tablet in the treatment of mild and moderate vulvovaginal candidiasis / 中华妇产科杂志

Objective:Using clotrimazole vaginal tablet as a positive control, to evaluate the results of clotrimazole vaginal expansion suppository in the treatment of mild and moderate vulvovaginal candidiasis in terms of efficacy, patient satisfaction, side effects, and recurrence rate.Methods:This study was jointly conducted by 5 hospitals from August 2017 to October 2018, patients with mild and moderate vulvovaginal candidiasis confirmed by fungal culture and symptoms scores were selected. They were randomized to experimental group and control group as 1∶1 ratio. In the experimental group ( n=105), the subjects applied clotrimazole vaginal expansion suppository (150 mg) daily at night for 7 days. In the control group ( n=106), the subjects used a single dose of clotrimazole vaginal tablet (500 mg). Follow-ups were performed at (8±3) and (30±5) days after the discontinuation of the drugs, respectively. The difference in clinical symptoms and signs scores was used to evaluate the improvement of clinical symptoms, and the patient′s satisfaction and side effects were recorded. Results:At the first follow-up, the experimental group and control group were followed up by fungal culture on the cure rate [66.7% (70/105) versus 63.2% (67/106), P>0.05] and total effective rate [98.1% (103/105) versus 99.1% (105/106), P>0.05], the differences were not statistically significant. At the second follow-up, the recurrence rates of the experimental group and the control group were 5.7% (4/70) and 14.9% (10/67), respectively, with no significant difference ( P>0.05). In the evaluation of patient satisfaction, the leakage of the drug in the experimental group was significantly better than that in the control group ( P<0.01). The side effects mainly included vaginal stimulation, itching and burning sensation, and there was no statistical difference between the two groups ( χ2=1.070, P=0.586). Conclusions:In the treatment of mild and moderate vulvovaginal candidiasis, clotrimazole vaginal expansion suppository is no less effective than clotrimazole vaginal tablet, and there is no significant difference in the recurrence rate between the two. In terms of patient satisfaction, clotrimazole vaginal expansion suppository is superior to clotrimazole vaginal tablet.

The vaginal microecology in gynecological outpatients: a report from China / 中华检验医学杂志

Objective To study the vaginal microecology of the patients in the outpatient department of Obstetrics and gynecology in China.Methods A multicenter cross-sectional study was conducted in gynecologic clinic of 9 collaborative hospitals in China.200 consecutive patients were collected in each hospital and their vaginal microecology combined with related factors were analyzed.Results A total of 2 093 specimens were collected in this study.The detection rate of Trichomonas was 5.5%(115/2 093). The detection rate of Candida mycelia was 15.9%(333/2 093), with germinal spores was 4.1%(86/2093).The detection rate of bacterial vaginosis was 18.8%(394/2 093).The distribution results of vaginal flora in patients showed that the normal flora accounted for only 27.3%(571/2 093).The normal flora with the insufficiency of H2O2 accounted for 23%(480/2 093).The bacteria inhibiting flora accounted for 3.8%(79/2 093).The abnormal microflora(non BV type)accounted for 14.9%(312/2 093).The abnormal microflora(BV intermediate type)accounted for 13.4%(280/2 093).The abnormal microflora(BV type)accounted for 17.6%(369/2 093).The average pH of vaginal discharge was 4.58 ±0.495.There was no significant difference of the incidence of trichomonas and bacterial vaginosis between north and south of the Yangtze river, while the detection rate of fungal hyphae and the fungal spores is significantly higher in the south than that in the north.The analysis results of factors affecting the microecology showed that age and contraception methods were two important factors.The patients′age from bacteria inhibition group was 49.64 +16.68 which was significantly higher than that of the other microecology groups.The proportion of abnormal microflora of patients from the oral contraceptive group was 40%(20/50).The proportion of abnormal microflora of patients from IUD group was 36.6%(63/172).Compared with these two contraception methods, the proportion of abnormal microflora of patients from condoms usage group was 27.8%(91/327)which was significantly lower.The incidence of abnormal leucorrhea in the normal group was 37.7%, which was significantly lower than that of other abnormal groups.Conclusion This study showed the vaginal microecology status of the Chinese outpatient ′s clinic and found that the vagina microecology was related to age, region and contraceptive methods.The typical manifestation of microecological abnormality is the increase of leucorrhea.(Chin J Lab Med,2018, 41:287-291)

Attach importance to female reproductive tract infection and vaginal microecological diagnosis and treatment in China / 中华检验医学杂志

Reproductive tract infection is an important part of systemic infection,and it has become a major social and public health problem in the world.Recent studies have shown that reproductive tract infection is closely related to tumor occurrence, infertility, ectopic pregnancy, premature rupture of membranes and premature delivery and so on.Almost all reproductive tract infections are accompanied by changes of genital tract microenvironment.The development of the vaginal microecological detection system and the application of the diagnosis platform for the lower genital tract make it possible toaccurately treat female genital tract infection.Therefore, more and more attention was also paid to the standardized test of female reproductive tract infection and vaginal microecology by experts and scholars in the related fields. (Chin J Lab Med,2018,41:251-253)

Efficacy and safety of low-dose levonorgestrel-releasing intrauterine system in Chinese women: a multicenter, single-arm, open labeled interventional trial / 中华妇产科杂志

Objective To evaluate the efficacy,bleeding profile and safety of low-dose levonorgestrel-releasing intrauterine system (LNG-IUS 8) in Chinese healthy women of childbearing age.Methods A multi-center,open-label,single-arm clinical trial conducted at 16 centres in China enrolled 773 healthy women of childbearing age (mean age 31.6 years old,range 18 to 40 years old),who demanded contraception,from April 2006 to June 2013.All women placed LNG-IUS 8 for 3 years and then been followed up at 3,6,9,12,18,24,30,36 months.The efficacy variables including pregnancy rate and expulsion rate were analyzed using life table,while observing adverse events (AE) to evaluate the safety.The bleeding profile happened during the study was assessed using 90-day reference intervals (World Health Organization criteria).Results Eight pregnancies occurred among 773 women,resulting in a overall Pearl index of 0.42 per 100 women years.The 3-year cumulative pregnancy rate was 0.37 per 100 women years and the 3-year cumulative expulsion rate was 1.99 per 100 women years.The number of women with bleeding/spotting reduced and the bleeding/spotting days declined over time.Totally 219 AE were reported related to LNG-IUS 8 placements.The most common AE were vaginal bleeding (8.2％,63/773)and the ovarian cyst (6.2％,52/773).LNG-IUS 8 had an improving effect on dysmenorrhea that the percentage of women with dysmenorrhea as well as the days of dysmenorrhea decreased over time.The percentage of women satisfied or very satisfied with LNG-IUS 8 was 87.2％ (622/713).Conclusion LNG-IUS 8 is highly effective and safe for Chinese healthy women of childbearing age.

Confocal laser scanning electron microscopy for assessment of vaginal Lactobacillus crispatus biofilm / 北京大学学报(医学版)

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 characteris-tics 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 adhe-sion occurred at h 4, which was in reversible attachment, then more and more Lactobacillus crispatus ag-gregated 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 bacte-ria was set up at h 24,with gradual matureation at h 24 to h 48. The biofilm dispersed at h 72. The bio-film 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 bio-film 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.

Expression of Notch1, Jagged1 and NICD in epithelial ovarian carcinomas and a preliminary study on the activity of gamma-secretase in epithelial ovarian carcinoma cell lines / 中华妇产科杂志

Objective To study the expression of Notch 1,Jagged1 and Notch intracellular domain (NICD) in epithelial ovarian carcinoma tissues and analyze the clinical significance.To explore the activity of γ-secretase in epithelial ovarian carcinoma cell line SKOV3 and the effect of N-[N-(3,5-dil uorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT),a γ-secretase inhibitor on the activity of γ-secretase in SKOV3.Methods Immunohistochemistry staining method was performed in 43 patients with epithelial ovarian carcinoma and 11 patients with benign epithelial ovarian tumor to detect the expression of Notch1,Jagged1 and NICD.The differences of expressionof Notch1,Jagged1 and NICD between malignant and benign ovarian tumors was compared and alsoanalyzed the correlation with clinicopathological parameters of ovarian carcinoma.Human serous ovarian cancer cell line SKOV3 and immortalized nontumorigenic ovarian epithelial cell line T29 were incubated in vitro.The activities of γ-secretase in SKOV3 and T29 with dimethyl sulfoxide (DMSO) and DAPT were detected respectively by Gal4VP16/UAS and dual luciferase reporter assay system.Results (1) The immunohistochemical composite scores (ICS) of Notch1 in epithelial ovarian carcinoma (6.7±2.2) were not significantly different with those in benign epithelial ovarian tumor (5.4± 2.7,P=0.153),while the ICS of Jagged 1 and NICD in epithelial ovarian carcinoma (5.3± 2.4,5.3± 2.3) were higher than those in benign epithelial ovarian tumor (1.6± 1.4,3.1± 1.7; all P＜0.01).The expression of Notch 1,Jagged 1 and N ICD had no correlation with patients' aged,history of carcinoma,ascites,the level of serum CA125,maximum length of ovarian tumor,Federation International of Gynecology and Obstetrics (FIGO) stage,grade and pathology subtypes (all P＞0.05).The hazard ratio between the high expression of Notch1,Jagged1,or NICD and the moderate to low expression of Notch1,Jagged1,or NICD,and Jagged1 were 0.771,1.648 and 1.316,respectively (all P＞0.05).The 5-year survival rate and median survival time between the high expression of Notch,Jagged 1 or NICD in subgroup and moderate to low expression in subgroup were of no difference (all P＞0.05).The activity of γ-secretase in SKOV3 was significantly higher than that in T29 [(12.2± 1.4)％,P=0.019].(2)After DAPT treated,the relative activity of γ-secretase in SKOV3 (50 μmol/L) was declined from (100.0±5.3)％ to (6.6±0.8)％ (P=0.001).Conclusions Jagged1 and NICD in Notch1 pathway may play a key role in the occurrence of ovarian carcinoma.The activity of γ-secretase in epithelial ovarian carcinoma was higher than that in ovarian epithelial cell which suggest that DAPT,γ-secretase inhibitor,may become the target of ovarian carcinoma treatment.

Results of different postoperative adjuvant therapies for stage Ⅰ b-Ⅱ a cervical carcinoma with risk factors / 中华妇产科杂志

Objective To investigate the effects of postoperative adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) or radiotherapy(RT) for Ⅰ b-Ⅱ a 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 Ⅰ b-Ⅱ a 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 Ⅰ b-Ⅱ a cervical carcinoma with risk factors.

Effect of 17α-hydroxyprogesterone caproate and medroxyprogesterone acetate on inflammation-induced preterm birth of mouse model / 中华围产医学杂志

Objective To study the effect of 17α-hydroxyprogesterone caproate (17P) and medroxyprogesterone acetate (MPA) on expression of tumor necrosis factor-α (TNF-α)and cyclooxygenase-2 (COX-2) in placenta and uterine myometrium of inflammation-induced preterm birth mouse model to investigate the mechanism of preventing inflammation-induced preterm birth by progestogen.Methods Thirty clean CD-1 mice were divided into 6 groups (5 mice in each group) at 15th day of gestation:control group,lipopolysaccharides (LPS) group,17P 1 mg+LPS group,17P 2 mg+ LPS group,MPA 1 mg+LPS group and dimethyl sulfoxide (DMSO) + LPS group.Progestogens at different dosage were administered 1 h before LPS and 6 h after LPS administration.After these mice were sacrificed,TNF-α and COX-2 levels in the myometrium and placenta were detected by real-time PCR and immunohistochemistry.Data were analyzed by ANOVA,and comparisons between groups were adopted LSD method.Results 1.The comparison of relative expression of COX-2 mRNA and TNF-α mRNA in myometrium and placenta among groups:(1) Expressions of COX-2 mRNA and TNF-α mRNA in myometrium and placenta in the study groups were obviously higher than those of control group (P＜0.05).(2) COX-2 mRNA expression in myometrium of 17P 1 mg+LPS group (11.410±3.931),17P 2 mg+LPS group (8.352±3.209) and MPA 1 mg+LPS group (11.920± 2.905) were obviously lower than that of LPS group (20.540± 4.147) and DMSO+ LPS group (18.620 ± 4.156) (P＜0.05,respectively) ; although TNF-α mRNAexpression had similar trends among these groups,there were no statistical significance (P＞0.05,respectively).(3) COX-2 mRNA expression in placenta of 17P 1 mg+LPS group (10.864±3.777),17P 2 mg+LPS group (7.084±1.667) and MPA 1 mg+LPS group (11.830±3.652) were obviously lower than that of LPS group (18.920±4.106) and DMSO+LPS group (23.820±7.554)(P＜0.05,respectively).(4) TNF-α mRNA expression in placenta in 17P 1 mg+LPS group (14.340±1.618),17P 2 mg+ LPS group (11.488 ± 2.910) and MPA 1 mg+ LPS group (13.040 ± 2.982) were obviously lower than that of LPS group (24.240±7.059) and DMSO+LPS group (23.040±5.896) (P＜0.05,respectively).2.The comparison of protein expression of COX-2 and TNF-α in placenta among groups:(1) The expression of COX-2 protein in placenta of the study groups was significantly higher than that of control group (P＜0.05).(2) There were no differences among the COX-2 protein expression of 17P 1 mg+ LPS group (14 360.92± 1766.01),17P 2 mg+ LPS group (13 340.18±965.35) and MPA 1 mg+LPS group (12 870.81±1521.97)(P＞0.05),while the COX-2 protein expressions of them were significantly lower than that of LPS group (16 426.64 ± 1823.87) and DMSO+LPS group (16 761.23±2388.17)(P＜0.05,respectively).(3) There were no differences among the TNF-α protein expression of 17P 1 mg+LPS group (22 750.96±4656.68),17P 2 mg+LPS group (22766.24± 3500.34) and MPA 1 mg+LPS group (20770.01±3318.48)(P＞0.05),while the TNF-α protein expressions of them were significantly lower than that of LPS group (26204.49±5090.34) and DMSO+LPS group (27346.18±3269.30)(P＜0.05,respectively).Conclusions 17P and MPA might prevent the preterm parturition of inflammation-induced mouse model by inhibiting inflammation cytokines and prostaglandins.

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 / 中华妇产科杂志

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.

Construction and verification of the prognostic model of ovarian serous adenocarcinoma / 肿瘤

Objective:To analyze the prognosis-related factors of ovarian serous adenocarcinoma in order to set up a prognostic model of serous adenocarcinoma and verify the effectiveness of the model as prognostic clinical criteria.Methods:The clinical, patholo-gical and follow-up data from 181 training samples with ovarian serous adenocarcinoma in Peking University First Hospital during January 1995 to December 2003 and another 42 detection samples with ovarian serous adenocarcinoma in Beijing Cancer Hospital during January 1999 to December 2005 were analyzed retrospectively. Kaplan-Meier univariate analysis was used to screen out prognostic factors; COX univariate and multivariate analyses were used to determine the risk coefficient of each factor and different layers in each factor; Pearson rank correlation analysis was used to identify the correlation of each factor. The prognostic model of ovarian serous adenocarcinoma was established on the conversion of risk coefficient to prognostic score and receiver operating characteristic (ROC) analysis was used to determine the cut-off value. The clinical data were collected to verify the sensitivity and specificity of the prognostic model based on the 3-year survival rate and Ki67 value.Results:The survival rate of patients with ovarian serous adenocarcinoma correlated with 6 factors including FIGO stage, histological grade, residual size, metastasis of lymph nodes, general condition after chemotherapy, and serum CA125 levels. The postoperative chemotherapy was an independent factor for prognosis. The prognostic model directly reflected the survival probability of classical COX risk ratio model, with higher score indicating lower survival probability and poorer prognosis. If combining prognostic score with Ki67 the sensitivity and specificity reached 64.7% and 96.0%, respectively.Conclusion:FIGO stage, histological grade, residual size, metastasis of lymph nodes, postoperative chemotherapy and serum CA125 were the prognostic factors of patients with ovarian serous adenocarcinoma. The prognostic model of ovarian serous adenocarcinoma can moderately reflect the actual survival status, and combination with Ki67 will increase the sensitivity and specificity.

Investigation of the situation of vaginal microflora in healthy women population / 中华妇产科杂志

Objective To assess the distribution of vaginal microflora in healthy women and investigate their cognition of lower reproductive tract infection-related knowledge as well as personal hygiene habits and character of behavior in seeking medical treatment. Methods Total of 1660 healthy women who had physical check-ups at the Medical Center of Renji Hospital were selected and received gynecologic examination, as well as routine examination, pH examination and bacterial culture of the vaginal discharge. In addition, 860 of them were randomly selected for questionnaire survey, in which reproductive tract infection -related knowledge and personal hygiene habits as well as behavior in seeking medical treatment were involved. Results Among the 1660 eensused women, vaginal average pH was 4. 16±0.21. The positive rate of Candida in vaginal discharge routine examination was 3.86% (64/1660), which was lower than that in aerobes culture 7.71% (128/1660). Candida alhicans was the most populous species 78.9% (101/128) ,followed by 7.8% (10/128) and 7.0% (9/128) for the Candida glabrata and Candida krusei respectively. The most populous species of vaginal microflora were hemolytic streptococcus A (63.80%, 1059/1660), Staphylococcus epidermidis (14.28%, 237/1660), and Enterococcus faecalis (D) group ( 11.44%, 190/1660). The questionnaire survey showed that 88.4% (760/860) of 860 women took active treatment when feeling unwell, 92.1% (792/860) of them had good hygiene practices, and only 21.2% (182/860) had the habit of vaginal douching. In addition, 50.0% (430/860) of them had the desire to obtain reproductive health knowledge through out-patient consultation. Conclusions Vulvovaginal Candida disease ranks the first in all types of vaginitis, among which, Candida albicans is the most populous species followed by the Candida glabrata and Candida krusei. Hemolytic streptococcus A and Staphylococcus epidermidis are the most common species of vaginal mieroflora in healthy women. The censused women have high awareness of reproductive health care and pay mueh attention to common gynecologic diseases such as lower reproductive tract infection. Nevertheless, we should strengthen the public education of reproductive health-related knowledge.

Study of local immunity of lower genital tract infections / 中华妇产科杂志

Objective To investigate the profile of local immunity of vagina and the immune defense mechanisms against lower genital tract infections. Methods Vaginal lavage was collected from healthy women and patients of vulvovaginal candidiasis, bacterial vaginosis, Trichomonol vaginitis, human papilloma virus infection(VVC), and chlamydia trachomatis infection. Each group included 60 cases. The level of interleukin (IL) 2,4,5, 13,8 and human defensin 5 (HD5) were detected by enzyme linked immunosorbent assay(ELISA). Results (1) Cytokine of helper T cell 1(Th1): the level of IL-2 between healthy women and VVC/ bacterial vaginosis (BV)/ trichomonol vaginitis (TV)/ chlamydia trachomatis (CT) patients had no significant difference. The IL-2 level(96±33 )×10-3 pg/L of human papilloma virus (HPV) infection patients was significantly higher than that of healthy women( P<0.05). (2)Cytokine of helper T cell 2 (Th2) : the level of IL-4 between healthy women and VVC/CT patients had no significant difference. The level of IL-5 between healthy women and BV patients had no significant difference. The IL-13 level(42±15)×10-3 pg/L of TV patients was significantly higher than that of healthy women (30±29)×10-3 pg/L (P<0.05). The IL-4 level (103±28)×10-3 pg/L of HPV infection patients was significantly higher than that of healthy women (36±22)×10-3 pg/L (P<0. 05 ). (3) IL-8 : the IL-8 level (5.8± 2.7) pg/L of TV infection patients was significantly higher than that of healthy women (2. 6±2.4) pg/L (P<0.05). The level of IL-8 between healthy women and BV patients had no significant difference. (4)HD5:the HD5 level of TV , BV, VVC, HPV and CT infection patients were significantly higher than that of healthy women (P<0.05). Conclusions (1) HD5 plays an important role in the defence of vaginal epithelial cell. (2) Th2 may be more important than Thl in lower genital tract infections.(3) IL-8 plays an important role in extrinsic source infections.

Expression of connexin 43 in ovarian cancer and its relationship with chemoresistance / 中华妇产科杂志

Objective To examine the expression of protein kinase C (PKC), connexin43(Cx43) and non-phosphorylated Cx43 in ovarian cancer, and discuss the role of phosphorylated of Cx43 in chemoresistance in ovarian cancer. Methods We examined the expression of Cx43, non-phosphorylated Cx43 and PKC in ovarian cancer tissue by immunohistochemistry, and compared their expression in chemosensitivity group and ehemoresistance group. Cisplatin resistant ovarian cancer cell line SKOV3/DDP cells were treated by staurosporine (a kind of PKC inhibitors). Then expression of Cx43, non-phosphorylated Cx43 and PKC were tested. Meanwhile, we tested chemosensitivity of SKOV3/DDP cells by ATP bioluminescence tumor chemosensifivity assay (ATP-TCA). Results (1) Immunohistochemically,the rates of positive expression of Cx43 and non-phospharylated Cx43 were 54%, 14% respectively in the chemoresistance group, which were 83%, 59% in the chemosensitivity group respectively (P<0.05). The rate of positive expression of PKC in 28 chemoresistance ovarian cancer cases (64%) was higher than that in 29 chemosensitivity cases (31% ,P<0.05). Both of them were significantly lower in ehemoresistanee group than in chemosensitivity group (P<0.05). In addition, the expression of PKC was negatively correlated with the expression of Cx43 and non-phosphorylated Cx43. The correlation coefficients were -0. 626 and -0. 714, respectively (P<0.05). (2) Immunohistochemically, PKC was down regulated, and Cx43 and non-phosphorylated Cx43 were up regulated in SKOV3/DDP cells after staurosporine treatment. The longer the staurosporine worked, the more expression of Cx43 was. (3) By ATP-TCA, SKOV3/DDP cells were resistant to paclitaxel and cisplatin. The tumor growth inhibition was higher in the group of paclitaxel or cisplatin combined staurosporine than in the group of paclitaxel or cisplatin alone. The sensitivity was intermediate in the group combined with low concentration staurosporine (1×10-8 moL/L), and the sensitivity was high in the group combined with high concentration staurosporine (1×10-7 mol/L). Conclusions Phosphorylation of Cx43 caused by PKC leads to decrease in the expression of Cx43. This effect makes ovarian cancer cells less chemosensitive. Phosphorylation of Cx43 caused by PKC can be inhibited by staurosporine.

Microecological investigation of vaginal microflora in women with varying degree gynecologic symptoms in clinics / 中华妇产科杂志

Objective To investigate the microecological status of vaginal microflora in the women with different vaginal symptoms. Methods From March 2006 to October 2007, 6982 cases with varying degree vaginal symptoms including pruritus, increaseed leucorrhea, the leucorrhea having unusual smell, in the gynecology outpatient department were studied. The vagina secretions were examined in terms of the pH value, the hydrogen peroxide test, and Gram dyeing inspection of vaginal bacteria and microecology appraisal for colony's density, the multiplicity, the superiority fungus, and the inflammatory response. Results Among 6982 patients, normal vaginal microecology was identified in 750 (10. 74%, 750/6982 );abnormal mieroeeology was found in 6232 ( 89. 26%, 6232/6982 ) ; bacterial vaginosis (BV) was detected in 729 (10. 44%, 729/6982);vulvovaginal candidiasis (VVC) was in 1527 ( 21.87%, 1527/6982 ). Ninety five patients (1.36% ,95/6982) were with both BV and VVC. Abnormal bacteria colonies were found in 1229(17. 60% ,1229/6982),and others were found in 2652(37. 98% ,2652/6982). Conclusions The vaginal microecology in the women with different vaginal symptoms can be either normal or abnormal. Microecology clinical evaluation system can assess the vaginal microecosystem.

Profile of serum soluble endoglin in pregnant women with severe pre-eclampsia and eclampsia / 中华妇产科杂志

Objective To discuss the serum endoglin expression in severe pre-eclampsia and eclampsia women and their relationships. Methods Forty-two severe pre-eclamptic patients and 4 eclamptic patients in Peking University First Hospital from Dec. 2005 to Dec. 2007 were enrolled in the study group, with the mean gestational week of 35 ± 4, the mean age of 29.3 ± 5.7 and the mean BMI (30.1 ± 4.1 ) kg/ m2. This group included 25 cases of early onset pre-eclampsia, 21 cases of late onset pre-eclampsia, 8 cases of fetal growth restriction and 5 cases of HELLP syndrome. The control group included 29 cases of normal pregnant women during the same period, with the mean gestational week of 33±4, the mean age of 30.7± 3.4 and the mean BMI(27.2±2. 2) kg/m2. Peripheral serum endoglin was determined by ELISA in these two groups. Results (1)There is positive correlation between serum soluble endoglin level and the gestational weeks during 27 to 37 gestational weeks in the control group (r=0.79, P<0.05), but there is no distinct relationship in the study group (r=0.31, P>0.05). (2) Serum endoglin level of severe pre-eclampsia group was higher than the normal group [(14.2±5.6)μg/L vs. ( 10.9 ± 4.2 ) μg/L, P<0.05]. (3) Serum endoglin level of early onset group did not differ from late onset group [(14.3±5.7)μg/L vs. (13.6±5.0)μg/L, P >0.05]. (4) No difference of serum endoglin between HELLP group and non-HELLP group was found [(10.1±2.9) μg/L vs. ( 14.4±5.4) μg/L, P>0.05 ]. (5) Serum endoglin level of FGR sub group was higher than non-FGR sub group [(17.3±6.1) μg/L vs. (13.0±4.8) μg/L, P < 0.05] in the stady group. Conclusion The elevated peripheral serum endoglin level may contributes to the pathogenesis of severe pre-eclampsia and FGR, but not the week of the onset of the disease.

Expression of Notch intracellular domain in cervical cancer and effect of DAPT on cervical cancer cell / 中华妇产科杂志

Objective To study the expression and clinical significance of Notch intracellular domain (NICD) in cervical cancer 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 of cervical cancer cell lines. Methods Western blot was used to detect the expression of NICD in the tissues of 40 cervical cancers and 21 normal cervix and its relationship with clinical features of cervical cancer was also analyzed. Proliferation of SiHa and HeLa cervical 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 SiHa and HeLa cells incubated with DAPT was detected by western blot. Results The expression level of NICD in cervical cancers was significantly higher than that of normal cervical tissues (1.237±0.353 vs 0.938±0.105, P<0.05). The NICD expression was higher in cervical cancers with high grade,lymph node involvement and parametrial invasion than that with low-middle grade (1.496±0.540 vs 1.150±0.216), without lymph node involvement (1.419±0.532 vs 1.159±0.210) and no parametrial invasion (1.718±0.710 vs 1.183±0.258), respectively (all P<0.05). The expression of NICD in cervical adenocarcinoma was higher than that of squamous cell cancer (1.463±0.395 vs 1.162±0.187, P<0.05). After SiHa and HeLa cells were incubated with DAPT, NICD expression was significantly lower than that in control (P<0.05). The effects of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells was depended on its concentrations and times. Conclusions NICD may play a key role in the occurrence and progress of cervical cancer. The mechanism of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells may be due to decreased the formation of NICD.

Pregnant outcomes and prognosis of women complicated with systemic lupus erythematosus / 中华围产医学杂志

Objective To understand the clinical features, management, pregnant outcomes and prognosis of pregnant women complicated with systemic lupus erythematosus (SLE). Methods Retrospective analysis of 34 women (35 pregnancies) complicated with SLE were conducted and 26 of them were followed up for 0.5～15 years. Results (1) Out of the 35 pregnancies in these 34 women, 8 were in remission stage, 8 in the well-controlled period, 1 in active phase and 18 were primary onset (10 diagnosed during the pregnancy, and 8 after terminations) during the pregnancy. (2) Among those diagnosed during the pregnancy, 2 women in the remission group and 3 in the well-controlled group were in the active stage of SLE. The several most common clinical manifestations indicating SLE deterioration were proteinuria, fatigue, edema, hypertension, erythra and decreased serum C3. (3) In women with onset during the pregnancy, 7 (38.9%) presented with proteinuria, edema and hypertension which similar to symptoms of gestational hypertension. (4) The average maternal age of the remission group was much older than those women with onset during pregnancy [(32.4±5.5) years vs (26.6±3.9) years, P=0.034]. while the proportion of active lupus nephritis was lower than that of the later (1/4 vs 16/16, P=0.004) and the well-controlled group (1/4 vs 6/6,P=0.033) during post-partum follow-ups. Conclusions Pregnancy prompted lupus nephritis has nothing to do with maternal age, but the stage of SLE. Patients who conceived in the remission stage are the least likely to have nephritic damage. Although women with onset during the pregnancy is relatively young, they are expected to have more serious renal damage and poor prognosis.

Clinical analysis of pregnancy complicated with cervical epithelial neoplasia-18 cases / 中华围产医学杂志

Objective To discuss the diagnosis,treatment and following-up of cervical intraepithelial neoplasia (CIN) during pregnancy.Methods Eighteen pregnant women with CIN,presented to the hospital from Jan.2004 to May.2008,were retrospectively reviewed.Pap smear,HPV,copolscopy and cervical biopsy were performed for diagnosis and all were followed up by Pap smear and copolscopy during pregnancy every 12 weeks,while 15 were followed up until 6-8 weeks postpartum.Results The incidence of CIN during pregnancy was 0.16%.All of the 18 women had abnormal Pap smear,followed by colopscopy and biopsy.Conservative management during the pregnancies every 3 months showed no progress in CIN.Among the 18 cases,17 delivered at term and only 1 preterm (36+4 weeks).Two out of the 18 women had normal delivery (11.1%),2 by forceps(11.1 %) and 14 by cesarean sections (77.8%).No neonatal apnea or neonatal respiratory distress syndrome had been observed.Pathological diagnosis was confirmed in all cases prenatally,including 4 CIN1,4 CIN2 and 10 CIN3.Four out of the 10 CIN3 remained after delivery,while 1 changed to CIN2.These 5 cases underwent leep electrical excision procedure and Pap smear results turned to normal at 6 to 11 months after delivery.One HSIL case were lost.The rest 4 CIN3 and all of the 8 CIN1 and CIN2 cases turned to normal or lesser degree.Fourteen of the 18 women received HPV test during pregnancy,and 12 (85.7%) were positive,among which 7 women were followed up at postpartum and 6 of them were HPV positive.Conclusions The three steps method for diagnosis of CIN during pregnancy is safe and effective.Conservative management of CIN during pregnancy is recommended.

Expression and function of cyclooxygenase-2 in endometrial carcinoma / 北京大学学报(医学版)

Objective: To evaluate the cyclooxygenase-2 ( COX-2) expression at mRNA and protein levels , as well as its clinical significance, and to study the correlation of COX-2 with angiogenesis, apoptosis and estrogen or progestron receptors. Methods: Forty-one samples of normal endoraetrium tissues and 52 ones of endometrial carcinomas( EC) were collected,together with their corresponding clinical information. RT-PCR was adopted to determine the expression of COX-2 mRNA. Immunohistochemical staining was engaged to evaluate the protein expression of COX-2, VEGF, Bcl-2 and the MVD marked by CD105. And TUNEL was used to count the apoptosis cells. Results: (1) Significantly higher mRNA and protein levels of COX-2 were found in endometrial carcinomas than in normal endometrial tissues ( P＜0.001) . (2) At protein level ,COX-2 expression was related to the grade(P =0.020) , but had nothing to do with the stage, pathological type, depth of myometrium invasion and lymph node metastasis. Neither did the level of COX-2 mRNA with all the factors above. (3)The level of COX-2 mRAN had nothing to do with that of protein(P =0. 125, r =0. 222). (4) The higher the expression of COX-2 protein was, the higher that of VEGF,MVD or Bcl-2 was,and the lower the count of apoptosis cells was P＜0.05. (6)The upregulation of COX-2 protein had no correlation with ER-α and ER-β . But it had positive correlation with PRA and PRB,P was 0.031 and 0.007 .respectively. Conclusion: (1)The expression of COX-2 is significantly higher in EC than in normal endometrium tissue, not only at the mRNA level, but also at protein level. ( 2 ) At protein level, COX-2 expression is related to the grade, but has nothing to do with the stage, pathological type, depth of myometrium invasion and lymph node metastasis. Neither does the level of COX-2 mRNA with all the factors above. (3)The upregulation of COX-2 protein in EC correlates with the increase of VEGF protein and MVD. (4) The upregulation of COX-2 protein in EC correlates with the increase of Bcl-2 protein and the decrease of apoptosis cells. (5)The upregulation of COX-2 protein in EC has no significant correlation with ER expression, but has something to do with the increase of PRA and PRB.

Investigate the Pathogen Flora and the Treatment of Recurrent Vulvovaginal Candidiasis / 实用妇产科杂志

Objective:To investigate the pathogen flora of recurrent vulvovaginal candidiasis(RWC),and to discuss its treatment. Methods: Fungal culture and susceptibility tests of vaginal discharge from 108 RWC patients were performed. Sensitive drugs were selected for effective consolidating treatment for half year. Fungal smears were examined at the 3rd and 6th months after the treatment respectively. Results:①Among RWC patients,there were 81 cas es of Candida albicans(75.0%), 19 cases of C. Glabrata(17.6%), 4 cases of C. Parapsilosis(3.7%) ,2 cases of C.tropicalis (1.9%) and 2 cases of M. Krusei (1.9%). The drug susceptibility test showed that 80.6% of these 108 patients were sensitive to nystatin; 66.7% were sensitive to clotrimazole; 65.7% were sensitive to miconazole; 57.4% were sensitive to fluconazole;8.3% were sensitive to ketoconazole;6.5% were sensitive to itraconazole; 7.4% were resistant to all of the above drugs.②The score of symptom and sign was significantly improved compared with the first visit at the 3rd and 6th month after the treatment( P<0.0001). The negative rate was 76.2%(80/105) at the 3rd month after the treatment and 64.8%(68/105)at the 6th month after the treatment. Conclusions:①The rate of non Candida albicans is increased to 25% in RWC patients, and 17.60% is Candida glabrata.②During the treatment of RWC, the drugs should be selected according to fungal culture, results of susceptibility test, medication experience of patients,and attack character. The research of immune abnormality of the local vagina will be helpful to improve the cure rate of RWC.